18 July 2012 print
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Study of orphan medicines market uptake finds substantial variation across Europe

An article appearing in the Journal of Clinical Pharmacy and Therapeutics reports observations on the variations in orphan medicinal product availability across Europe, examining how two particular factors affect the market uptake of orphan products: gross domestic product (GDP) and the availability of a formal Health Technology Assessment (HTA)-organisation to inform reimbursement and policy decisions. Analysing sales data from 23 EU countries between 2001 and 2010, using the IMS Health database, the authors looked at the numbers of drugs launched and the sales and volume uptake of 17 selected orphan medicines. Countries with a higher GDP enjoyed a greater availability of orphan drugs, independent of the existence of an HTA-organisation. For countries with a lower GDP, those that have an HTA-organisation had a lower rate of orphan drug availability. The study reveals the wide heterogeneity in HTA practice amongst the EU Member States and suggests that initiatives such as the CAVOMP (Clinical Added Value of Orphan Medicinal Products) project, a recommendation for which is currently being adopted by the European Union Committee of Experts on Rare Diseases, could help facilitate the uptake of orphan drugs across Europe.
Learn more


EUCERD update
Executive Summary from the 5th Meeting of the European Union Committee of Experts on Rare Diseases now online

The Executive Summary of the Fifth Meeting of the European Union Committee of Experts on Rare Diseases, which took place 20-21 June 2012, is now available online.

OrphaNews Europe will be back in early September. We take this opportunity to wish all our readers a pleasant and relaxing summer.


EU Policy News
New brochure highlighting EU health projects includes examples from the field of rare diseases

A new brochure, produced by the Executive Agency for Health and Consumers (EAHC) in collaboration with DG Sanco, showcases a selection of projects that demonstrate the “… contribution of the Health Programme to the development and implementation of national policies and public health programmes across the European Union”. The document Working Together to Improve Public Health in Europe presents 29 case studies from each of the European Union Member States, as well as Norway and candidate-country Croatia. In the domain of rare diseases, the Orphanet presence in the Czech Republic is highlighted. Orphanet, the rare disease and orphan drug reference information portal with partners in 38 countries, originated in France in 1997. A partnership with the Czech Republic was forged in 2006. The brochure selection describes the various services Orphanet provides and the role of the Orphanet-Czech Republic team in compiling a list of the resources available nationally, including specialised clinics, medical laboratories, ongoing research, registries, clinical trials, patient organisations, and data on rare diseases. There is also a selection outlining the role Bulgaria has played in the European Project for Rare Diseases National Plans Development (Europlan). As one of the early countries to adopt a national plan for rare diseases, Bulgaria has contributed experience to other countries beginning the process of developing a strategy for their rare disease patients.
Consult the document Working Together to Improve Public Health in Europe


National & International Policy Developments
New publication from the WHO summarises rare disease activities and revision of the International Classification of Diseases
The Bulletin of the World Health Organization has published an article that offers readers an overview of the situation for rare disease patients and summarises many of the ongoing activities in the fields of information, awareness raising, research, therapeutics and more. Particular emphasis is given to initiatives at the EU-level and the recently-formed International Rare Disease Research Consortium (IRDiRC). Mention is also given to the Topic Advisory Group for Rare Diseases of the World Health Organization, charged with the enormous task of ensuring that all rare diseases will be appropriately and clearly represented in the revision of the International Classification of Diseases (ICD). This process has been particularly challenging due in large part to a lack of a specific structure and corresponding tools for the reconciliation of disparate views gathered from the various expert groups contributing to the revision process of the ICD. Rare diseases figure in nearly all chapters of the ICD and it is estimated that the presence of code-specific rare diseases will increase from the current number of less than 500 to over 6000 in the revised ICD. The experts involved in coordinating this momentous effort are keen on finding a way forward, as a revised ICD with the correct representation of rare diseases will do much to capture much-needed knowledge in the field of epidemiology, allowing policy makers around the world to adapt strategies accordingly.
Consult the WHO article

New collaboration will bring insight into the early origin and development of rare diseases
A new collaboration in the USA will focus on research and treatments for young children. The National Institutes of Health (NIH) and the NIH Clinical Center are joining forces with the Children’s National Medical Center to create the Translational Research in Pediatrics Program. According to a press release, the NIH Clinical Center, which sees more rare disease patients than any other facility in the USA, typically cares for children weighing more than 20 pounds (9.071 kilogrammes) and/or older than two years of age. The new programme will allow investigators to intervene by developing studies for rare conditions at an earlier age, allowing for “greater insight into early origin and development of disease and discovery of new treatments for rare disorders”. In the press release, NIH Clinical Center Director John I. Gallin, MD, is quoted as saying: “We are grateful that Children's National is opening its doors to help us expand our research profile and establish new partnerships between our institutions that will make a difference in the lives of young children suffering from rare, and often life-threatening, diseases".
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Other European news
UK rare disease patients take ownership of their medical records
A unique patient-controlled electronic medical records system has formed a partnership with the rare disease patient advocacy group Alkaptonuria (AKU) Society and the Royal Liverpool University Hospital to help AKU patients better manage their healthcare and lead more independent lives. Patients Know Best, a commercially available online tool, permits patients to organise, manage and control their health care provisions while also facilitating physician access to secure, online consultations. In a press release, Dr. Nicolas Sireau, Chairman of the AKU Society describes the "constant struggle" of the rare disease patient to coordinate their medical records between different healthcare professionals: “Patients are often the experts in their own condition and the partnership we’ve signed with Patients Know Best will empower patients to control access to their medical records and share them with relevant clinicians at the right time”. Patients Know Best is integrated into the National Health Service’s secure network in the UK and is already being used by clinical teams with their patients in the UK, Europe and the Middle East.
Learn more

Other International News
A study of Middle Eastern paediatric beta-thalassaemia patients shows that delaying iron chelation leads to a lower quality of life
An open-access article appearing in BMC Blood Disorders looks at the health related quality of life for children in the Middle East with beta-thalassaemia. Beta-thalassaemias are a group of hereditary blood disorders characterised by anomalies in the synthesis of the beta chains of haemoglobin resulting in variable phenotypes. Three main forms have been described: thalassaemia major, thalassaemia intermedia and thalassaemia minor. Individuals with thalassaemia major usually present within the first two years of life with severe anaemia, requiring regular red blood cell transfusions. Findings in untreated or poorly transfused individuals with thalassaemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Health Related Quality of Life (HRQoL) attempts to measure and/or describe a patient’s “perceptions of the impact of disease and treatment on their physical, psychological and social functioning and well-being”. In this article, the authors describe a cross-sectional study using the Pediatric Quality of Life Inventory (PedsQL) with 60 affected children from Kurdistan, Palestine, Libya, Iraq and Syria. Only 22% of the children received regular transfusion support. Some 78% of patients had hepatomegaly, due in a majority of cases to chronic hepatitis B or C. The assessment investigated both the children’s perceptions as well as the parents’, revealing that parents often slightly underestimate their child’s HRQoL. The central finding of the study shows that a delayed start of iron chelation is linked to a negative impact on total PedsQL score, which measures physical, emotional, social and school functioning. The authors call for an effort to raise parents’ awareness and knowledge levels in developing countries in order to improve the HRQoL in affected children.
Consult the open access article

Guidance Documents and Recommendations
EuroGentest2 seeks feedback on prenatal diagnostics guidelines
EuroGentest2 is a Coordination Action funded by the 7th Framework of the European Commission. The project considers all aspects of genetic testing. A EuroGentest2 expert workshop on prenatal diagnosis was held in May 2012, producing a first draft of guidelines. These guidelines are organised into four sections: objective of prenatal diagnostic testing, general principles underpinning prenatal diagnostic testing, logistical issues involved in testing and topics for counselling in prenatal diagnosis. Open for consultation, comments for the guidelines are sought from any relevant organisation or interested person. The deadline for submitting comments is 15 August 2012.
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Ethical, Legal & Social Issues
Laboratoires CTRS to pursue its case for marketing authorisation for Orphacol despite unfavourable ruling from the EU Court of Justice
As was reported in the 20 June 2012 issue of OrphaNews Europe, the application for marketing authorisation for Orphacol (cholic acid), an orphan-designated medicinal product indicated for the treatment of inborn errors of primary bile acid synthesis, was rejected by the European Commission, on the grounds that the application was incomplete, lacking pre-clinical and clinical evidence, despite two separate favourable opinions recommending marketing authorisation from the EMA's Committee for Medicinal Products for Human Use. The EU Member States vetoed the Commission’s request to reject marketing authorisation and the case went before the EU Court of Justice. The sponsor of Orphacol, France-based Laboratoires CTRS (Cell Therapies Research & Services) deposited an application: for a declaration that the Commission failed to act in unlawfully failing to adopt a final decision in relation to the applicant’s application for a marketing authorisation for the medicinal product Orphacol, and, in the alternative, for annulment of the decision, allegedly contained in the Commission’s letter of 5 December 2011, not to grant that authorisation to the applicant . On 4 July, a ruling was issued by the EU Court of Justice, dismissing the application for a declaration of failure to act as inadmissible. However, the court ordered the European Commission to bear its own costs and to also pay those incurred by CTRS. CTRS is not ready to cede and is preparing to pursue the case further.
Consult the Judgement

Haemophilia: justifying the cost of a rare disease treatment
The authors of an article appearing in the journal Haemophilia assert that policy makers should take into account societal preferences, in addition to standard cost-effectiveness, when making distributional decisions for haemophilia prophylaxis. Haemophilia is a rare inherited disease characterised by spontaneous haemorrhage or prolonged bleeding due to factor VIII or IX deficiency. Amongst the reasons why society may be willing to pay for costly haemophilia prophylaxis, is the nature of the disease. The authors hypothesise that as an inherited illness not brought on by lifestyle factors, society might be more willing to pay for treatment. Additionally, as a disease that affects children, the authors cite studies that suggest higher priority is given to treatments for children. The rarity of haemophilia is another characteristic that might make society favourable toward treatment and studies are cited that suggest society places a greater value on health gains made by individuals when there are a small number of cases. The characteristics of the treatment may also make society value prophylaxis, in that it is considered a preventive treatment, one that averts the damage and disability induced by haemophiliac bleeding. Lastly, the costs involved in ensuring the safety of the treatment could be valued, in view of the history of haemophilia treatment, particularly during the period when haemophilia patients were exposed to a lack of safety measures in their blood product treatments.
Consult the PubMed abstract


Orphanet News
Orphanet joins forces with patientINFORM to enrich its rare disease information offer

In order to provide timely access to the most relevant information on rare diseases, Orphanet furnishes links to the summaries of journal articles and clinical practice recommendations selected for their quality and published by recognised professionals. The major obstacle to providing the full text for these articles is obtaining permission from copyright holders. Now, via a new partnership with patientINFORM, a collaborative private-sector initiative of medical publishers, health organisations, medical societies, and health information professionals, Orphanet can more easily enrich its content through direct, free-access links to relevant studies, reviews, guidelines and recommendations published in the medical and scientific literature. The goal of patientINFORM is to allow patients, their family members and anyone interested in learning more about a specific disease or its treatment to access new research articles through the web sites of participating health organisations or publishers. The new partnership between Orphanet and patientINFORM means that Orphanet can offer more full texts on relevant rare disease topics from the participating publishers providing access to such articles.
Learn more about patientINFORM


New Syndromes

Facial dysmorphism associated with developmental delay in two patients with a 7p22.1 microduplication
A publication dated May 2011 reports on a 28 month-old patient presenting with speech delay, large anterior fontanel, as well as particular facial features, i.e. prominent forehead, anteverted nares, ocular hypertelorism, low-set and posteriorly rotated ears with a left preauricular pit, wide-spaced and pegged teeth. The patient also displayed mild kyphosis, bilateral bridged palmar creases, broad thumbs, and an undescended left testis. Behavior, fine and gross motor development were appropriate for age. The authors found the smallest interstitial 7p duplication reported to date, and does not include genes previously implicated as candidates for a 7p duplication syndrome. The article suggests that this duplicated interval contains one or more genes implicated in skeletal maturation, craniofacial development, and speech acquisition. An even smaller 7p22.1 duplication is mentioned in an article dated January 2012, detected in a 14.5 year-old patient with similar facial dysmorphism and a mild intellectual disability, fully overlapping with the above-cited duplication. Among the 15 RefSeq genes included in this locus, the authors draw attention to ACTB encoding β-actin which they consider a good candidate for the disturbance of craniofacial development.
Consult the PubMed abstracts

AmJMedGenetA ; 2508-11 ; October 2011
AmJMedGenetA ; 1200-3 ; May 2012
A syndromic form of primary erythermalgia due to a SCN9A mutation probably also inducing a distal limb under-development
The authors describe a kindred with clinical features of small fiber neuropathy manifesting with distal pain, together with an acromesomelic phenotype of small forearms, hands, lower legs, and feet. One member of this family also presents with dysautonomia symptoms such as profound sweating, bowel disturbances, episodic dry eyes and mouth, hot flashes, and erectile dysfunction. All affected subjects carry a novel missense mutation in the SCN9A gene encoding sodium channel NaV1.7. SCN9A mutations are known to induce primary erythermalgia. As for the syndromic form encountered here, the authors hypothesize that the mutant channels produce, on the one hand, dorsal root ganglion neuron hyperexcitability causing erythermalgia and, on the other, a small peripheral nerve fiber dysfunction that may contribute to distal limb under-development.
Consult the PubMed abstract

Brain ; 345-58 ; February 2012
Marfanoid habitus, inguinal hernia, advanced bone age, and distinctive facial features suggesting a new collagenopathy
The authors report on two sibs, a girl and a boy born to consanguineous parents, with a marfanoid habitus, myopia, inguinal hernia, advanced bone age, and many particular facial features, mainly downslanting of the palpebral fissures, ptosis and everted lower eyelids, and everted vermilions. However, may be due to their young age, they don’t fulfil the criteria for a diagnosis of Marfan syndrome since they don’t present cardiovascular, pulmonary and skin manifestations. Moreover molecular analysis of the Marfan syndrome associated genes, i.e. FBN1, FBN2, TGFBR1, and TGFBR2, is normal. Given that the authors also had to rule out other diagnoses suggested by these clinical features such as Ehlers–Danlos syndrome types VI and VIIC, they conclude that this could be a new syndrome, perhaps a collagenopathy.
Consult the PubMed abstract

AmJMedGenetA ; 1185-9 ; May 2012
A new leukoencephalopathy manifesting with two forms identified in 12 patients with EARS2 mutations disturbing mitochondrial DNA translation
The authors have identified a new neurological disease in 12 patients all sharing an early onset and rapidly progressive mitochondrial leukoencephalopathy with thalamus and brainstem involvement showing typical MRI features and high lactate in body fluids. Clinically patients can be divided into two groups, severe and mild. The severe form is characterized by lack of psychomotor development and hypotonia soon after birth and then by spastic tetraparesis, dystonia, visual impairment and seizures. Patients later stabilise but remain severely disabled and exhibit persistent lactate levels elevation. The clinical onset of the mild form is most often observed during the second half of the first year of life and it manifests with spasticity, loss of milestones and sometimes seizures and extreme irritability. Improvement occurs from the second year on and lactate declines in body fluids. All 12 patients carry mutations of EARS2 encoding mitochondrial glutamyl-tRNA synthetase therefore likely to disrupt mitochondrial DNA translation.
Consult the PubMed abstract

Brain ; 1387-94 ; May 2012
GUCY2C mutations found in patients with intestinal dysfunctions point to the GC-C – CFTR pathway as a potential mediator of some gastrointestinal diseases
A family with a dominantly inherited, fully penetrant syndrome of chronic mild diarrhea of early onset and dysmotility is evaluated in an article published on March 2012. Some of the 32 affected members of this family also suffer from other conditions such as Crohn’s disease, small-bowel obstruction, and esophagitis with or without esophageal hernia. A heterozygous activating mutation in GUCY2C encoding guanylate cyclase C (GC-C) has been found in all affected subjects. The authors conclude that “increased GC-C signaling disturbs normal bowel function and appears to have a proinflammatory effect, either through increased chloride secretion or additional effects of elevated cellular cGMP”. GUCY2C mutations have also been identified in newborns of two unrelated consanguineous kindreds affected by meconium ileus and described in a publication dated April 2012. In these patients, intestinal obstruction is not associated with cystic fibrosis, in contrast to a large part of meconium ileus, and the mutations are homozygous and induce a drastic reduction or a total absence of the GC-C activity. These findings point to the GC-C – CFTR pathway as a potential mediator of gastrointestinal diseases such as Crohn’s disease, small-bowel obstruction, irritable bowel syndrome, and cystic fibrosis-like intestinal phenotype.
Consult the PubMed abstracts

N Engl J Med ; 1586-95 ; 26 April 2012
Am J Hum Genet ; 893-9 ; May 2012

Dystonin-related disorders: a new hereditary sensory autonomic neuropathy resembling familial dysautonomia but more severe
The authors describe a new hereditary sensory autonomic neuropathy (HSAN) identified in 3 infants of a consanguineous family presenting with clinical features characteristic for familial dysautonomia (absent tearing, blotching, feeding difficulties, absent deep tendon reflexes, and abnormal histamine test with no axon flare) but with a more severe nature since distal contractures, a motionless with open-mouth facies, severe psychomotor retardation, and early death are also observed. Autopsy on a fetus after an interrupted pregnancy in the same family suggests that it was affected by the same disorder. Familial dysautonomia (FD) is associated with IKBKAP anomaly but, here, the identified mutation affects DST encoding dystonin, a protein overexpressed in familial dysautonomia. This DST mutation results in an instable transcript with a loss of its microtubule binding capacity. The authors think that both dystonin-related HSAN and FD are linked with a microtubules disorganization that may be mitigated in FD.
Consult the PubMed abstract

Ann Neurol ; 569-72 ; April 2012
A novel X-linked disorder associating a chromosomal duplication with autism features and a global developmental delay
Searching for gene copy number variations predisposing to autism spectrum disorders, the authors have studied 3 cases in a family with a pedigree classical for X-linked inheritance. All 3 boys have severe autism in a context of global developmental delay and multiorgan involvement. This phenotype is associated with a Xq12-q13.3 duplication and thus may be mediated by increased dosage of genes located in this duplication such as OPHN1, AR, EFNB1, GJB1, MED12, TAF1, and NLGN3, a gene known to cause autism when abnormal.
Consult the PubMed abstract

Ann Neurol ; 498-508 ; April 2012
A new disproportionate short stature syndrome with hypotrichosis and peculiar facial features
The authors describe 8 individuals from two unrelated consanguineous families with adult height ranges from 112 cm to 127 cm due to pre and post-natal growth retardation, which probably manifests as early as the second trimester of pregnancy. Their stature is not only short but also disproportionate since they present with clinodactyly, brachydactyly, small hands, hypoplastic fingernails, short long bones, especially the femurs and humeri, with mild metaphyseal changes and very short femoral necks. They also have hypotrichosis and peculiar facial features. According to the authors, this condition doesn’t fulfill the diagnostic criteria of any known disorder of disproportionate short stature. Therefore they conclude that it is a new syndrome inherited in an autosomal recessive pattern.
Consult the PubMed abstract

Eur J Med Genet ; 256-64 ; April 2012
First evidence of involvement of the 12S rRNA A1555G mutation in a mitochondrial syndromic deafness associated with hypertension
The authors studied two Chinese families carrying the homoplasmic 12S rRNA A1555G mutation until now known to induce non syndromic hearing loss in the maternal lineage. However, among 21 matrilineal relatives of these two families, 9 present with both hearing loss and hypertension, 2 have only hypertension and one just suffers from hearing loss. The symptoms appear during adulthood and their severity is variable. One more peculiarity of these two pedigrees is that they belong to the Eastern Asian haplogroup D5a when the A1555G mutation occurred in other mtDNA haplogroups. According to the authors, it is the first evidence that this mtDNA mutation can result in both hearing loss and hypertension. Nevertheless the 12S rRNA mutations generally cause mild mitochondrial dysfunctions suggesting that the A1555G mutation is necessary but not sufficient to induce this clinical phenotype and that other modifier factors might also be involved. A previously described TRMU A10S mutation modulating the phenotypic expression of the A1555G mutation in Israeli and European families was sought, but not found in affected members of these two Chinese families.
Consult the PubMed abstract

Eur J Hum Genet ; 607-12 ; June 2012

New Genes

Autosomal recessive primary microcephaly: a CEP135 mutation disturbing centrosomal function confirms the role of centrosome in the disease
Consult the PubMed abstract
To read more about "Autosomal recessive primary microcephaly"

Am J Hum Genet ; 871-8 ; 4 May 2012
Hydranencephaly: a newly identified NDE1 deletion widens the spectrum of brain malformations caused by NDE1 mutations
Consult the PubMed abstract
To read more about "Hydranencephaly"

Neurogenetics ; Epub ahead of print ; 15 April 2012
Saldino-Mainzer syndrome: a ciliopathy caused by IFT140 mutations
Consult the PubMed abstract
To read more about "Saldino-Mainzer syndrome"

Am J Hum Genet ; 864-70 ; 4 May 2012
Syndromic intellectual deficit/Dubowitz syndrome: homozygous mutations in NSUN2, a gene encoding an RNA methyltransferase, are responsible in some families
Consult the PubMed abstracts
To read more about "Dubowitz syndrome"

Am J Hum Genet ; 847-55; 856-63 ; 4 May 2012
J Med Genet ; 380-5 ; June 2012
Auriculo-condylar syndrome: mutations of PLCB4 and GNAI3 encoding endothelin pathway signaling enzymes induce an homeotic transformation
Consult the PubMed abstract
To read more about "Auriculo-condylar syndrome"

Am J Hum Genet ; 907-14 ; 4 May 2012
Acrofacial dysostosis, Nager type is genetically heterogeneous and most cases seem to be induced by mutations in SF3B4, a component of the spliceosome
Consult the PubMed abstract
To read more about "Acrofacial dysostosis, Nager type"

Am J Hum Genet ; 925-33 ; 4 May 2012
Idiopathic aplastic anaemia and myelodysplastic syndromes: identification of SRP72 mutations, altering protein translocation and processing
Consult the PubMed abstract
To read more about "Idiopathic aplastic anemia"
To read more about "Myelodysplastic syndromes"

Am J Hum Genet ; 888-92 ; 4 May 2012
Cervical dystonia: CIZ1 mutations found in an adult onset primary form that may result from a neurodevelopmental abnormality of cerebellar Purkinje cells
Consult the PubMed abstract
To read more about "Cervical dystonia"

Ann Neurol ; 458-69 ; April 2012
Autosomal recessive hereditary distal motor neuropathy: HSJ1 chaperone loss-of-function involved in a form predominantly affecting lower limbs
Consult the PubMed abstract
To read more about "Autosomal recessive hereditary distal motor neuropathy"

Ann Neurol ; 509-19 ; April 2012
Arrythmogenic right ventricular dysplasia: lamin A/C mutations found in severe forms provide evidence that desmosomal proteins are not the only ones involved
Consult the PubMed abstract
To read more about "Arrhythmogenic right ventricular dysplasia"

Eur Heart J ; 1128-36 ; May 2012
DNMT1 neuropathies: autosomal dominant cerebellar ataxia, deafness and narcolepsy linked with exon 21, sensory loss with dementia and hearing loss with exon 20
Consult the PubMed abstract
Hum Mol Genet ; 2205-10 ; 15 May 2012
AGK mutation found in non-syndromic congenital cataract: the first anomaly of a lipid metabolism component to be implicated in a yet unknown manner
Consult the PubMed abstract
To read more about "Non-syndromic congenital cataract"

Hum Mutat ; 960-2 ; June 2012
Walker-Warburg syndrome: ISPD mutations disrupting glycosylation of laminin-binding dystroglycans are a common cause
Consult the PubMed abstracts
To read more about "Walker-Warburg syndrome"

Nat Gen ; 575-80; 581-5 ; May 2012
UV-sensitive syndrome: UVSSA mutations impair transcription-coupled nucleotide-excision repair through destabilization of the RNA Pol II complex
Consult the PubMed abstracts
To read more about "UV-sensitive syndrome"

Nat Gen ; 586-92; 593-7; 598-602 ; May 2012
Common variable immunodeficiency: CD21 and LBRA mutations cause hypogammaglobulinemia due to B cells defects
Consult the PubMed abstracts
To read more about "Common variable immunodeficiency"

J Allergy Clin Immunol ; 801-810 ; March 2012Am J Hum Genet ; 986-1001 ; 8 June 2012

Familial clubfoot with or without associated lower limb anomalies: PITX1 mutations involved in a broad spectrum of lower-limb malformations
Consult the PubMed abstract
To read more about "Familial clubfoot with or without associated lower limb anomalies"

Eur J Hum Genet ; 705-8 ; June 2012
Systemic sclerosis: CAV1 joins the list of susceptibility genes
Consult the PubMed abstract
To read more about "Systemic sclerosis"

Ann Rheum Dis ; 1034-41 ; June 2012
Dehydrated hereditary stomatocytosis: mutations in FAM38A encoding PIEZO1, a subunit of mechanosensory ion channels, may disturb erythrocyte volume regulation
Consult the PubMed abstract
To read more about "Dehydrated hereditary stomatocytosis"

Blood ; Epub ahead of print ; 23 April 2012
B-cell non-Hodgkin lymphoma: a gene fusion between TBL1XR1 and TP63 exclusively detected in cases with the germinal center B-cell-like subtype
Consult the PubMed abstract
To read more about "B-cell non-Hodgkin lymphoma"

Blood ; 4949-52 ; 24 May 2012
A duplication including the IHH locus induces a phenotype belonging to the same clinical spectrum as acrocallosal and Greig cephalopolysyndactyly syndromes
Consult the PubMed abstract
To read more about "Acrocallosal syndrome"
To read more about "Greig cephalopolysyndactyly syndrome"

Eur J Hum Genet ; 639-44 ; June 2012
NIPA1 polyalanine repeat expansions increase the risk of developing amyotrophic lateral sclerosis, bring forward the age of onset and shorten survival
Consult the PubMed abstract
To read more about "Amyotrophic lateral sclerosis"

Hum Mol Genet ; 2497-502 ; 1 June 2012
Peroxisome biogenesis disorder: a PEX11β mutation altering peroxisome division with effects no detectable by standard laboratory investigations
Consult the PubMed abstract
To read more about "Peroxisome biogenesis disorder"

J Med Genet ; 307-13 ; May 2012
GRIP1 mutations cause classic Fraser syndrome
Consult the PubMed abstract
To read more about "Fraser syndrome"

J Med Genet ; 303-6 ; May 2012
Bardet-Biedl syndrome: marked developmental anomalies associated with a mutation in LZTFL1 that regulates ciliary trafficking of BBSome and Shh signalling
Consult the PubMed abstract
To read more about "Bardet-Biedl syndrome"

J Med Genet ; 317-21 ; May 2012
Deafness – intellectual deficit, Martin-Probst type: a mutation in the gene encoding the RAB40AL disrupts the cytoplasmic localization of this Rab GTPase
Consult the PubMed abstract
To read more about "Deafness - intellectual deficit, Martin-Probst type"

J Med Genet ; 332-40 ; May 2012
Primary ciliary dyskinesia: CCDC103 mutations cause defects in dynein arms assembly that impair cilia motility
Consult the PubMed abstract
To read more about "Primary ciliary dyskinesia"

Nat Genet ; 714-9 ; June 2012
Haploinsufficiency of KANSL1, a regulator of histones acetylation, causes 17q21.31 microdeletion syndrome
Consult the PubMed abstracts
To read more about "17q21.31 microdeletion syndrome"

Nat Genet ; 636-8; 639-41 ; June 2012
Pontocerebellar hypoplasia type 1: mutations in EXOSC3 suggest a role of the RNA exosome in the survival of cerebellar and spinal motor neurons
Consult the PubMed abstract
To read more about "Pontocerebellar hypoplasia type 1"

Nat Genet ; 704-8 ; June 2012
Hereditary mixed polyposis syndrome: a duplication that may induce tumorigenesis through increased and ectopic expression of GREM1 reducing BMP signalling
Consult the PubMed abstract
To read more about "Hereditary mixed polyposis syndrome"

Nat Genet ; 699-703 ; June 2012
Hamamy syndrome: alterations in the homeodomain of IRX5 cause defective craniofacial, blood, heart, bone and germ cell development
Consult the PubMed abstract
Nat Genet ; 709-13 ; June 2012
Hepatocellular carcinoma: major role for SWI/SNF chromatin remodeling complexes and involvement of interferon and oxidative stress pathways
Consult the PubMed abstract
To read more about "Hepatocellular carcinoma"

Nat Genet ; 694-8 ; June 2012
Multiple epiphyseal dysplasia, Al-Gazali type expand the clinical spectrum associated with mutations in KIF7, a regulator of Hedgehog signalling
Consult the PubMed abstract
To read more about "Multiple epiphyseal dysplasia, Al-Gazali type"

Orphanet J Rare Dis ; 7(1):27 ; 15 May 2012

Research in Action

A new approach to pre-clinical research could boost academic and small enterprise orphan drug development
A new article appearing in the Orphanet Journal of Rare Diseases offers readers A generalizable pre-clinical research approach for orphan disease therapy. The authors propose a method that “relies on databases and computational analyses prior to the more expensive experimental validation of potential therapies”. Such an approach could side-step some of the costs and time of preclinical research. Access to “system-wide datasets, compounds and reagents for the orphan disorder research community, advances in both systems biology and computational prediction of small molecule-macromolecule interaction, the identification of additional generalizable therapeutic approaches” and further collaboration are listed as key steps for moving forward this approach.
Consult the open-access article

Orphanet J Rare Diseases ; 7:39 ; 15 June 2012
Fundamental Research
Autosomal recessive limb-girdle muscular dystrophy type 2H is underlain by premature senescence mediated by accumulation of PIAS4 in a mouse model
Consult the PubMed abstract
To read more about "Autosomal recessive limb-girdle muscular dystrophy type 2H"

J Clin Invest ; 1764-76 ; 1 May 2012
Cystic fibrosis : susceptibility to meconium ileus is associated with SNPs in genes encoding apical plasma membrane constituents
Consult the PubMed abstract
To read more about "Cystic fibrosis"

Nat Gen ; 562-9 ; May 2012
Ataxia-telangiectasia: dephosphoryled when ATM kinase is deficient, HDAC4 translocates to the neuronal nucleus where its accumulation is toxic
Consult the PubMed abstract
To read more about "Ataxia-telangiectasia"

Nat Gen ; 783-90 ; May 2012
Huntington disease: protective effect of XBP1 silencing in mice could be due to FoxO1 induction of autophagic destruction of mutant Htt
Consult the PubMed abstract
To read more about "Huntington disease"

Hum Mol Genet ; 2245-62 ; 15 May 2012
Facioscapulohumeral dystrophy: an epigenetic deregulation due to D4Z4 deletion reversing the expression of the Polycomb and Trithorax groups
Consult the PubMed abstract
To read more about "Facioscapulohumeral dystrophy"

Cell ; 819-31 ; 11 May 2012
Peripartum cardiomyopathy results from excess anti-angiogenic signalling that can be worsened by pre-eclampsia or multiple gestation
Consult the PubMed abstract
To read more about "Peripartum cardiomyopathy"

Nature ; 333-8 ; 17 May 2012
KCTD13 dosage during early neurogenesis is closely related to head size phenotypes associated with 16p11.2 microdeletion and microduplication syndromes
Consult the PubMed abstract
To read more about "16p11.2 microdeletion syndrome"
To read more about "16p11.2 microduplication syndrome"

Nature ; 363-7 ; 17 May 2012
T-cell large granular lymphocyte leukemia: Patients with STAT3 mutations presented more often with neutropenia and rheumatoid arthritis
Consult the PubMed abstract
To read more about "T-cell large granular lymphocyte leukemia"

N Engl J Med ; 1905-13 ; 17 May 2012
Amyotrophic lateral sclerosis: an in vitro model of the familial form from human embryonic stem cells overexpressing a mutant superoxide dismutase 1
Consult the abstract
To read more about "Amyotrophic lateral sclerosis"

Stem Cells Trans Med ; 396-402 ; May 2012
Clinical Research
Kawasaki disease: addition of prednisolone to intravenous immunoglobulin improves coronary artery outcomes in severely affected Japanese patients
Consult the PubMed abstract
To read more about "Kawasaki disease"

Lancet ; 1613-20 ; 28 April 2012
Glioblastoma: transplanted P140K-expressing hematopoietic stem and progenitor cells protect against myelosuppression due to alkylating chemotherapy
Consult the PubMed abstract
To read more about "Glioblastoma"

Sci Transl Med ; 133ra57 ; 9 May 2012
Prevent, recognize and manage silent cerebral infarcts, the most common neurologic injury in affected children with sickle cell anemia
Consult the PubMed abstracts
To read more about "Sickle cell anemia"

Blood ; 3684-90 ; 19 April 2012
Blood ; 4587-96 ; 17 May 2012
Smith-Lemli-Opitz syndrome results in typical cranofacial features appearing from neonatal period in all cases and more obvious in the more severely affected
Consult the PubMed abstract
To read more about "Smith-Lemli-Opitz syndrome"

Am J Med Genet A ; 1020-8 ; May 2012
Romano-Ward syndrome: high risk for life-threatening events due to mutations in cytoplasmic loops of the KCNQ1 channel are reduced by β-blocker therapy
Consult the PubMed abstract
To read more about "Romano-Ward syndrome"

Circulation ; 1988-96 ; 24 April 2012
Risk of hypertension significantly elevated in male premutation carriers with Fragile X-associated tremor/ataxia syndrome
Consult the PubMed abstract
To read more about "Fragile X-associated tremor/ataxia syndrome"

Am J Med Genet A ; 1304-9 ; June 2012
PHACE syndrome: locus 7q33 provides a genetic susceptibility to phenotypic expression with other confounding genetic or environmental factors
Consult the PubMed abstract
To read more about "PHACE syndrome"

Am J Med Genet A ; 1363-7 ; June 2012
SAPHO syndrome: short-term efficacity of anakinra, an interleukin 1 receptor antagonist, in five of six patients
Consult the PubMed abstract
To read more about "SAPHO syndrome"

Ann Rheum Dis ; 1098-1100 ; June 2012
Primary amyloidosis : good hematologic response and improvement in organ function in one bitherapy and four tritherapy studies
Consult the PubMed abstracts
To read more about "Primary amyloidosis"

Blood ; 4387-90; 4391-4 ; 10 May 2012
Blood ; 4860-7 ; 24 May 2012
Blood ; 5384-90; 5397-404 ; 7 June 2012
Diffuse large B-cell lymphoma: Helicobacter pylori eradication therapy is effective in the treatment of early-stage H pylori-positive gastric pure form
Consult the PubMed abstract
To read more about "Diffuse large B-cell lymphoma"

Blood ; 4838-44 ; 24 May 2012
American trypanosomiasis: questioning the efficacy on heart function of transplantation of autologous bone marrow–derived mononuclear cells
Consult the PubMed abstract
To read more about "American trypanosomiasis"

Circulation ; 2454-2461 ; 22 May 2012
Soft tissue sarcomas: pazopanib, an angiogenesis inhibitor, can be an option after previous chemotherapy against metastatic non-adipocytic form
Consult the PubMed abstract
To read more about "Soft tissue sarcoma"

Lancet ; 1879-86 ; 19 May 2012
Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyneuropathy: mitigated results
Consult the PubMed abstract
To read more about "Chronic inflammatory demyelinating polyneuropathy"

Lancet Neurol ; 493-502 ; June 2012
Cystic fibrosis: estradiol levels correlated with infective exacerbations among menstruating women infected by Pseudomonas aeruginosa
Consult the PubMed abstract
To read more about "Cystic fibrosis"

N Engl J Med ; 1978-86 ; 24 May 2012
Stem Cells

Acute liver failure improved in mice by human amniotic fluid mesenchymal stem cells and hepatic progenitor-like cells revealing high anti-inflammatory activity
Consult the PubMed abstract
To read more about "Acute liver failure"

Gut ; 894-906 ; June 2012
Pneumococcal meningitis: neuronal precursors grafted into hippocampus migrate into the injured area where they differentiate into functional neurons in rats
Consult the PubMed abstract
To read more about "Pneumococcal meningitis"

Stem Cells ; 1206-15 ; June 2012
Amyotrophic lateral sclerosis: promising intraspinal transplantations of autologous bone marrow mononuclear cells or neural stem cells
Consult the PubMed abstracts
To read more about "Amyotrophic lateral sclerosis"

Stem Cells ; 1144-51; 1277-85 ; June 2012
Gene Therapy
Mucopolysaccharidosis type 6: γ retroviral therapy allows expression of a functional sulfatase but doesn't reduce all clinical manifestations in cats
Consult the PubMed abstract
To read more about "Mucopolysaccharidosis type 6"

Mol Ther ; 898-907 ; May 2012
Glial tumor: replication-competent herpes simplex virus retargeted to HER2, highly expressed in high-grade glioma, kills cancer cells in mice
Consult the PubMed abstract
To read more about "Glial tumor"

Mol Ther ; 994-1001 ; May 2012
Wiskott-Aldrich syndrome: lentiviral gene therapy provide benefits that need to be balanced with some adverse side effects
Consult the PubMed abstract
To read more about "Wiskott-Aldrich syndrome"

Blood ; 4395-407 ; 10 May 2012
Junctional epidermolysis bullosa, Herlitz type: early intra-amniotic gene transfer using lentiviral vector improves skin blistering phenotype in a murine model
Consult the PubMed abstract
To read more about "Junctional epidermolysis bullosa, Herlitz type"

Gene Ther ; 561-9 ; May 2012
Duchenne muscular dystrophy: rescue of dystrophin expression with AAV-antisense mediated exon skipping approach using snRNAs in mice
Consult the PubMed abstract
To read more about "Duchenne muscular dystrophy"

Hum Mol Genet ; 2559-71 ; 1 June 2012
Leber hereditary optic neuropathy: gene delivery with AAV modified to target mitochondria rescues ATP synthesis and suppresses visual loss in mouse model
Consult the PubMed abstract
To read more about "Leber hereditary optic neuropathy"

PNAS ; E1238-47 ; 15 May 2012
Aromatic L-aminoacid decarboxylase deficiency: improvement of symptoms with AADC gene delivery in the putamen using AAV
Consult the PubMed abstract
To read more about "Aromatic L-aminoacid decarboxylase deficiency"

Sci Transl Med ; 134ra61 ; 16 May 2012
Therapeutic Approaches
In addition to being an urea-cycle disorder, argininosuccinic aciduria is also a NO deficiency susceptible to improvement by long-term NO supplementation
Consult the PubMed abstract
To read more about "Argininosuccinic aciduria"

Am J Hum Genet ; 836-46 ; 4 May 2012
Congenital muscular dystrophy type 1A: Losartan, an angiotensin II type I receptor blocker, improves fibrosis via TGF-β and MAPK pathways in mice
Consult the PubMed abstract
To read more about "Congenital muscular dystrophy type 1A"

Ann Neurol ; 699-708 ; May 2012
Acquired thrombotic thrombocytopenic purpura: ADAMTS13 variants with modified spacer domain resist auto-antobodies while enhancing their VWF cleavage activity
Consult the PubMed abstract
To read more about "Acquired thrombotic thrombocytopenic purpura"

Blood ; 3836-43 ; 19 April 2012
Infantile neuronal ceroid lipofuscinosis: blood-brain barrier integrity improved in mice by anti-differentiation effect of resveratrol upon TH17 lymphocytes
Consult the PubMed abstract
To read more about "Infantile neuronal ceroid lipofuscinosis"

Hum Mol Genet ; 2233-44 ; 15 May 2012
Duchenne muscular dystrophy: upregulation of utrophin in brain doesn't compensate for effects of dystrophin loss upon mouse intellectual capacities
Consult the PubMed abstract
To read more about "Duchenne muscular dystrophy"

Hum Mol Genet ; 2263-76 ; 15 May 2012
Propionic acidemia: an in vitro study shows more or less efficacy of a readthrouh drug in suppressing nonsense mutations affecting PCC expression
Consult the PubMed abstract
To read more about "Propionic acidemia"

Hum Mutat ; 973-80 ; June 2012
Progression of Rett syndrome arrested in a mouse model by the phagocytic activity of wild-type microglia
Consult the PubMed abstract
To read more about "Rett syndrome"

Nature ; 105-9 ; 5 April 2012
Congenital stationary night blindness: restoration of functional rod-mediated vision after photoreceptor precursors transplantation in a mouse model
Consult the PubMed abstract
To read more about "Congenital stationary night blindness"

Nature ; 99-103 ; 3 May 2012
Leiomyosarcoma: antibodies inhibiting CD47 enable phagocytosis of cancer cells by macrophages in mice and in human cells
Consult the PubMed abstract
To read more about "Leiomyosarcoma"

PNAS ; 6656-61 ; 24 April 2012
Cutaneous neuroendocrine carcinoma: transcriptional inhibition of survivin preferentially kill carcinoma cells infected with Merkel cells polyomavirus
Consult the PubMed abstract
To read more about "Cutaneous neuroendocrine carcinoma"

Sci Transl Med ; 133ra56 ; 9 May 2012
Blocking micro RNA-155 expression in mice prevents lethal acute graft versus host disease after allogeneic hematopoietic stem cell transplant
Consult the PubMed abstract
To read more about "Graft versus host disease"

Blood ; 4786-97 ; 17 May 2012
Metachromatic leukodystrophy: enzyme replacement therapy less effective than HSC transplantation in early stages in an aggravated old mouse model
Consult the PubMed abstract
To read more about "Metachromatic leukodystrophy"

Hum Mol Genet ; 2599-609 ; 1 June 2012
Localized epidermolytic palmoplantar hyperkeratosis: personalized RNAi therapy better than generic to target the mutant allele rather than the wild-type
Consult the PubMed abstract
To read more about "Localized epidermolytic palmoplantar hyperkeratosis"

J Invest Dermatol ; 1627-35 ; June 2012
Fanconi anemia: combining a mitochondrial protective agent with an antioxidant decreases chromosome instability in lymphocytes in vitro
Consult the PubMed abstract
To read more about "Fanconi anemia"

Orphanet J Rare Dis ; 7(1):28 ; 16 May 2012
Nephroblastoma: Wilms tumor cells respond to IGFR1 signaling in an orthotopic xenograft model
Consult the PubMed abstract
To read more about "Nephroblastoma"

PNAS ; E1267-76 ; 15 May 2012
Medulloblastoma: tumor reduction and increased survival in mice with an Hedgehog pathway inhibitor that does not induce resistance due to genetic mutations
Consult the PubMed abstract
To read more about "Medulloblastoma"

PNAS ; 7859-64 ; 15 May 2012
Diagnostic Approaches

Creutzfeldt-Jakob disease: CSF concentrations of cAMP and cGMP and RT-QuIC analysis helpful in establishing diagnosis and monitoring disease progression
Consult the PubMed abstract for the first article
Consult the abstract for the first article

To read more about "Creutzfeldt-Jakob disease"

PLoS One ; e32664 ; March 2012
Ann Neurol ; DOI: 10.1002/ana.23589 ; Advance online publication
Retinitis pigmentosa: next-generation sequencing approach to help diagnosis of a very heterogeneous disease
Consult the PubMed abstract
To read more about "Retinitis pigmentosa"

Hum Mutat ; 963-72 ; June 2012
Hereditary nonpolyposis colon cancer is best detected by routine molecular screening than with the Bethesda guidelines
Consult the PubMed abstract
To read more about "Hereditary nonpolyposis colon cancer"

Gut ; 865-72 ; June 2012

Patient Management and Therapy

Enthesitis-related arthritis: new advances in juvenile spondyloarthritis
Consult the PubMed abstract
To read more about "Enthesitis-related arthritis"

Nat Rev Rheumatol ; 269-79 ; May 2012
Proximal spinal muscular atrophy types 1,2 and 3: no drug treatment has been proven to have significant efficacy
Consult the PubMed abstracts
To read more about "Proximal spinal muscular atrophy type 1"
To read more about "Proximal spinal muscular atrophy type 3"
To read more about "Proximal spinal muscular atrophy type 2"

Cochrane Database Syst Rev ; CD006281 ; 18 April 2012
Cochrane Database Syst Rev ; CD006282 ; 7 December 2011
Primary brain tumors in adults: a review
Consult the PubMed abstract
Lancet ; 1984-96 ; 26 May 2012
Neuromyelitis optica: the role of aquaporin 4
Consult the PubMed abstract
To read more about "Neuromyelitis optica"

Lancet Neurol ; 535-44 ; June 2012
About progressive non fluent aphasia
Consult the PubMed abstract
To read more about "Progressive non-fluent aphasia"

Lancet Neurol ; 545-55 ; June 2012
Idiopathic pulmonary fibrosis: increased risk of death and hospitalization with treatment combining prednisone, azathioprine, and N-acetylcysteine
Consult the PubMed abstract
To read more about "Idiopathic pulmonary fibrosis"

N Engl J Med ; 1968-77 ; 24 May 2012

Courses & Educational Initiatives

Epidermolysis Bullosa – An Introduction and Advanced Management courses
Two training days devoted to Epidermolysis Bullosa are being held at the Great Ormond Street Hospital (London in September 2012. The first, an Introductory Day, will be delivered by the EB Specialist Nurses at Great Ormond Street Hospital, and colleagues from St Thomas's Hospital. The programme will offer an overview of the different types of epidermolysis bullosa, (EB) multi disciplinary management and expected outcomes. It is suitable for community children’s nurses; nurses working in palliative care; and dermatology nurses. Learn more
The second day-long course, Advanced Management, will offer a greater understanding of the complexities and complications of EB and their management. It is geared towards medical practitioners working with adults and children with EB and will allow attendees to discuss the current research and current / potential therapies; recognise complications pertaining to the different types of EB; explain principles of general care of the patient with EB; describe current treatments and symptom management; and more. Learn more

Goldrain Courses in Clinical Cytogenetics and Prenatal Genetic Diagnosis
The Sixth Clinical Cytogenetics course will be held from 15-21 September 2012 at the Goldrain Castle in South Tyrol (Italy). The lectures are aimed at both clinicians and cytogeneticists who have strong mutual interests in both fields. To best profit from the lectures and exercises, participants should have at least one year of practical experience in laboratory and/or clinical cytogenetics.
The Goldrain Prenatal Genetic Diagnosis, tentatively course scheduled from 6-12 October 2012, is aimed at both obstetricians and clinical and laboratory geneticists who have strong mutual interests in each other’s field. In order to have the maximum profit from the lectures and exercises, participants should have at least one year of practical experience in prenatal obstetric diagnosis and/or clinical genetics. Besides the lectures, there is room for discussions, student presentations, and at the end a non-compulsory multiple-choice examination.
For further details

IberoAmerican Course for the Multidisciplinary Study of Movement Disorders: Parkinson Disease and Spinocerebellar Ataxias
This international workshop will held in Lima, Peru from 19-20 September 2012. The course is aimed at neurology residents and students in a doctoral degree program in medicine, biology, biochemistry, biotechnology, pharmacy, genetics, or related disciplines. This course will provide updates on the current knowledge in basic, clinical, and translational research, genetics, and therapeutics in movement disorders such as Parkinson disease and the Spinocerebellar Ataxias.
For further details

Online Master of Science in Haemoglobinopathy
A unique opportunity for health professionals to specialise in the field of haemoglobinopathies online with minimum disruption to professional and personal lives. The course has been designed to meet the needs of a wide range of medical professionals, including medical graduates interested in haemoglobinopathy (general physicians, specialists such as paediatricians, haematologists, clinical geneticists, obstetricians/gynaecologists, behavioural scientists); science graduates interested in medical research related to haemoglobinopathy and genetics; and other healthcare professionals interested in haemoglobinopathy – such as counsellors, clinical psychologists, nurse specialists and midwives.
For further details

The European School of Haematology distance learning tools
The European School of Haematology (ESH) is a non-profit organisation founded in 1986. Its mission is continuous medical education in Haematology and the fields related to Haematology. ESH organises conferences throughout Europe and on other continents. It also produces distance learning tools of which many are freely available on the ESH website: These include: The Curriculum on Iron Metabolism and Related Disorders: This is a comprehensive curriculum comprising webcasted lectures, videos, interviews, round table discussions etc. The faculty is composed of distinguished international experts in the field. Webcasted conferences are also freely available on the website, including topics such as: Diagnosis and Management of Rare Anaemias; Haemoglobin Disorders: Laboratory Diagnosis and Clinical Management; World Cord Blood Congress, and more.
Orphan Academy 2012 Programme
The Orphan Europe Academy provides healthcare professionals with the opportunity to increase knowledge, develop new ideas and strengthen scientific collaboration by offering training and educational activities for healthcare professionals involved in the diagnosis and management of patients affected by rare diseases.
For further details

EuroGentest Quality Management and Accreditation/Certification of Genetic Testing Workshops
The European network of excellence for all aspects of genetic testing, EuroGentest, under its Quality Management and Accreditation/Certification of Genetic testing Workgroup, has several training workshops available around Europe in coming months that focus on accreditation and quality assurance.
For further details


What's on Where?

3rd Annual Orphan Drug Summit
Date: 25-26 July 2012
Venue: London, UK

This commercial event will bring together industry leaders from pharma/biotech companies, patient advocacy groups, government, regulators, investors and insurance companies, to share approaches, challenges and successes in orphan drug development.
For further details

7th European Elastin Meeting
Date: 1-4 September 2012
Venue: Ghent, Belgium

Topics include mechanisms of microfibrils and elastic fibres, heritable and acquired diseases, therapeutic advances and more.
For further details

13th International Workshop on Multiple Endocrine Neoplasia
Date: 5-8 September 2012
Venue: Liege, Belgium

An established event for all those interested in research and treatment of multiple endocrine neoplasias, this workshop represents the ideal opportunity to share knowledge with peers and those working in related fields. Both research techniques and therapeutic modalities have undergone significant expansion in recent years and the program provides an opportunity for all to inform and be informed about thought-provoking advances in treatment, genetics and molecular biology.
For further details

The 13th International Meeting on Human Genome Variation and Complex Genome Analysis (HGV2012)
Date: 6-8 September 2012
Venue: Shanghai, China

Scientific sessions include: Beyond GWAS; Impact of 1,000 Genomes Project; Genome variation in complex diseases; Rare variations in neuropsychiatric and developmental disorders; New technologies; Challenges and Opportunities of large datasets; Therapeutic Targets Emerging from Genetic Variants in Common Networks; and much more.
For further details

First International Symposium on the Ehlers-Danlos Syndrome
Date: 8-11 September 2012
Venue: Ghent, Belgium

Topics include natural history; clinical aspects; updated nosology; diagnostics guidelines; therapeutic and management strategies; animal models, and more.
For further details

Joint DIA/ EFGCP/ EMA Medicines for Children Conference on Development of Paediatric Medicines: From Learning to Adapting
Date: 26-27 September 2012
Venue: London, UK

The aim of this conference is to discuss paediatric drug development in Europe, offering open discussion between academics, clinicians, regulatory authorities, patient associations and the pharmaceutical industry.
For further details

15th Biennial Meeting of the European Society for Immunodeficiencies
Date: 3-6 October 2012
Venue: Florence, Italy

The conference will cover the following topics: Inflammation; Immune Dysregulation; Innate Immunity; Hemophagocytic Lymphohistiocytosis; Immunotherapy; Networking for PID; Diagnostics of Combined Immunodeficiencies; Increasing Awareness of PID Worldwide; New Frontiers on PID Therapeutics; Gene Therapy; Autoimmunity in PID; New Developments in Transplantation; Mechanism of Humoral Dysregulation in PID; B Cell Disorders; Immunodeficiency Secondary to Autoantibodies: Phenocopies of PID; Thymus Defects; and DNA Repair and Telomere Defects. The XIIth Biennial Meeting of the International Patient Organisation for Primary Immunodeficiencies (IPOPI) is also being held in partnership with the European Society for Immune Deficiency (ESID), and the International Nurses Group for Immune Deficiency (INGID).
For further details

Mechanisms of Intellectual Disability: From Genes to Treatment
Date: 3-7 October 2012
Venue: Roscoff, France

The conference will cover the following topics: Genetics and Epigenetics of cognition and intellectual disorders; Cloning and characterization of genes; RNA metabolism and ID; Structures and plasticity of synapses and ID; Neurogenesis and synaptogenesis; Migration, interneurons and ID; Neuronal circuit development and ID ; and Towards a cure: lessons from animal models.
For further details

EpiRare International Workshop: Rare Disease and Orphan Drug Registries
Date: 8-9 October 2012
Venue: Rome, Italy

The International Workshop “Rare Diseases and Orphan Drug Registries” is organised in the framework of the EpiRare project (“European Platform for Rare Disease Registries”, co-funded by EU Commission, DG SANCO). Open to scientists, clinicians, patient associations, policy makers and enterprises, the workshop aims to share different experiences of rare disease registration in Europe and beyond; highlight the strengths and opportunities of linking rare disease registration activities, orphan drug post-marketing surveillance, etc; promote the sustainability and networking of registration activities; and more. Deadline for abstract submission: 31 July 2012
For further details

Second International Conference on Esophageal Atresia: From the Fetus to the Adult
Date: 8-9 October 2012
Venue: Montreal, Canada

In addition to bringing together experts from various disciplines, the theme of the conference will create important links between paediatric and adult medicine, reflecting the need for a continuum of care, which this increasingly numerous population requires. Inherent morbidity related to this condition also underlines the need for long-term monitoring.
For further details

Orphan Drugs & Rare Diseases Conference
Date: 8-9 October 2012
Venue: London, UK

This commercial event will present briefings from opinion leaders, including those with hands-on experience of regulating new drug discoveries, companies who have already developed advanced orphan drugs and been granted orphan designation, and selected experts in the field. Speakers will offer insights into expanding the reach of medicine to previously untreatable and unreachable patients with rare diseases; different regulatory and policy environments; new drug discoveries; innovative business strategies and funding models, and the importance of partnerships with patient groups and those at the point-of-care.
For further details

15th Society for the Study of Behavioural Phenotypes International Research Symposium and Education Day: Social Phenotypes in Genetic Disorders
Date: 11-13 October 2012
Venue: Leuven, Belgium

The theme of this year's conference is "Social Phenotypes in Genetic Disorders" and the focus will be on the development, phenotype, genetics and brain basis of social cognitive skills, and on molecular targeted therapy in genetic syndromes. Deadline for abstract submission: 31 May 2012
For further details

3rd Pan-European Conference on Haemglobinopathies and Rare Anaemias: Towards the Future
Date: 24–26 October 2012
Venue: Limassol, Cyprus

The Thalassaemia International Federation is delighted to announce the organisation of the 3rd Pan-European Conference, held under the auspices of the Cyprus Presidency and in close collaboration with the Cyprus Ministry of Health. The conference will bring together stakeholders to discuss avenues of action to tackle the growing public health burden of chronic and rare diseases in Member States and the EU.
For further details

The Second Joint International Symposium on Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation
Date: 26–27 October 2012
Venue: Ede, Netherlands

Topics will include autophagy; clinical studies; erythropoiesis; new genes; pathophysiology; protein-misfolding; treatment strategies and round table discussions with patient organisations and basic and clinical researchers.
For further details

International Ataxia Research Conference
Date: 1-3 November 2012
Venue: London, UK

Topics will include emerging therapeutic strategies for the ataxias; genetic and molecular analysis of the frataxin gene and protein; episodic ataxias and non-inherited ataxias; ataxia clinical research from trials to clinic – biomarkers and clinical trials; and more. .
For further details

8th International Society for Newborn Screening European Regional Meeting
Date: 4-6 November 2012
Venue: Budapest, Hungary

Topics will include: To screen or not to screen - setting up screening panels; Congenital adrenal hyperplasia; Cystic fibrosis; Severe combined immune deficiencies; Lysosomal storage disorders; and more.
For further details

6th International Symposium on Childhood MDS and Bone Marrow Failure syndromes
Date: 7-9 November 2012
Venue: Prague, Czech Republic

Topics will include Refractory Cytopenia of Childhood, advanced MDS; Juvenile Myelomonocytic Leukemia; Ph-negative Myeloproliferative Disorders; Therapy-related myeloid neoplasia; Severe Aplastic Anemia; Congenital Bone Marrow Failure; Morphology and Classification; Stem cell biology; Molecular aberrations and potential targets; Novel therapeutics, and Hematopoietic Stem Cell Transplantation.
For further details

3rd Annual World Orphan Drug Congress
29 - 30 November 2012
Geneva, Switzerland

The 3rd annual World Orphan Drug Congress provides a forum for the rare disease industry. This commercial event has three dedicated tracks this year: clinical development and R&D; market access, pricing, and reimbursement; corporate development and partnerships.
For further details

10th Asia-Pacific Conference on Human Genetics
Date: 5-8 December 2012
Venue: Kuala Lumpur, Malaysia

The APCHG2012 will examine various themes on personalised medicine, human variations in the Asia-Pacific region as well the latest advances on genetic diagnostics and technology and their implications to healthcare in the region. In addition, the APCHG2012 will also discuss issues pertaining to bioethics, genetics education and counselling as well as preventative strategies for birth defects and inborn errors of metabolism, and to provide a platform for patients and families to discuss emerging issues in individuals with inherited conditions and chronic disabilities.
For further details

7th Alstrom Syndrome International Family Conference and Scientific Symposium
Date: 9-13 May 2013
Venue: Massachusetts, USA

Medical professionals and scientists will hold Symposia on Thursday, 9 May and Saturday 11 May.
For further details

8th International Prader-Willi Syndrome Conference
Date: 17-21 July 2013
Venue: Cambridge, UK

An opportunity for all involved worldwide in research, working or living with people with PWS to present current research and explore best practice in clinical and day to day management of PWS.
For further details


Media, Press & Publications

Considering issues of privacy and consent in biobanking
A special issue of Public Health Genomics focuses on key issues in biobanking. Biobanks are of special interest in the field of rare diseases, where scattered patients and research resources make sharing data and samples crucial to moving forward understanding and treatment. The contents of this issue address the topics of consent, privacy, security and other current challenges.
Title: Privacy, Data Protection and Responsible Government: Key Issues and Challenges in Biobanking
Author : P Dabrock -Ed
Publisher: Karger, June 2012
ISBN-13: 978-3805599962

Clinical Pharmacology and Therapeutics journal addresses rare disease and orphan drug research topics
A series of articles, published in Clinical Pharmacology and Therapeutics, address issues relating to rare disease research and orphan drug development. The Role of Academic Institutions in the Development of Drugs for Rare and Neglected Diseases describes the evolving role of university-driven research for rare disease treatments in closing the innovation gap in the biopharmaceutical industry, caused in large part by increasing costs. With industry shifting to later-stage drug developing, academia is in a unique position to provide discovery and early stage research. Academia and industry complement each other and together can accelerate the process of developing new therapies for rare diseases.

Another interesting article appearing in the same journal provides a Quantitative Analysis to Guide Orphan Drug Development by employing pharmacometric techniques. Pharmacometrics is described as “…a science that involves the quantitative analysis of data resulting from clinical trials and encompasses exposure–response models, quantitative drug–disease-trial models, clinical trial simulations, and enrichment or adaptive study designs. Pharmacometrics is frequently mechanism based, if the cause of disease is well known and the drug target and mechanism of action are well understood. Its primary objective is to inform decisions”. The author demonstrates how quantitative analysis of data at the descriptive, mechanistic, and systems levels can constitute a rational approach to orphan drug development.

A third article reviews the state of Gene, Stem Cell, and Future Therapies for Orphan Diseases. Advanced therapies offer hope for rare diseases that presently have no treatment. Gene therapy and stem cell therapy, as well as a possible combination of both approaches by the genetic modification of stem cells, hold promise for treating or potentially curing certain rare diseases.

Raising Orphans: How Clinical Development Programs of Drugs for Rare and Common Diseases Are Different compares orphan and nonorphan medicinal products approved in the USA for the treatment of endocrine, haematologic, pulmonary, and neurologic diseases. While this study provides quantitative evidence to the conjecture that clinical development programmes are smaller for orphan products than for conditions with a higher prevalence, with orphan drug trials having about one-sixth the number of participants as non-orphan studies, the authors nonetheless conclude that: "Substantial evidence of treatment benefit may be demonstrated in relatively small clinical trials of targeted therapies for orphan diseases. This may be driven by the ability to identify specific points of intervention (i.e., genetic defects) that may be addressed by specific targeted therapies, thereby resulting in high response rates and clinically relevant improvements in end points. Conversely, clinical development programs for medicines to treat more nonorphan disorders commonly include heterogeneous populations, and therapeutic intervention is less likely to be targeted to a specific defect".

Finally, the article Optimizing Drug Outcomes through Pharmacogenetics: A Case for Preemptive Genotyping presents an analysis of six well-characterised drug therapies with known severe adverse effects and estimates the number of adverse events that could potentially be prevented using a preemptive pharmacogenetic genotyping strategy that includes patient medication exposure information combined with variant allele frequencies, overall adverse event rates, and excess risk estimates from published data. The Orphanet rare disease information database includes several entries of adverse effect conditions, including some with pharmacogenetic profiles.
Consult the table of contents


Orphanews Europe, the newsletter of the European Union Committee of Experts on Rare Diseases
Orphanews Europe is supported by the European Commission's DG SANCO (EUCERD Joint Action N° 2011-22-01)
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Louise Taylor
Contact Us
Editorial Board: Ségolène Aymé, Kate Bushby, Catherine Berens, Helena Kaariainen, Odile Kremp, Yann Le Cam, Jordi Llinares-Garcia, Antoni Montserrat, Catherine Pouzat, Charlotte Rodwell, Jaroslaw Waligora

EUCERD Country Representatives: Helmut Hintner (Austria), Pol Gerits (Belgium), Radka Tincheva (Bulgaria), Ivo Baric (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek Jr. (Czech Republic), Marianne Jespersen (Denmark), Inna Vabamae (Estonia), Helena Kaariainen (Finland), Alain Garcia (France), Birgit Schnieders (Germany), Christos Katamis (Greece), Janos Sandor (Hungary), Thor Thorarinsson (Iceland) , John Devlin (Ireland), Bruno Dallapiccola (Italy), Antra Valdmane (Latvia), Romalda Baranauskiene (Lithuania) , Yolande Wagener (Luxembourg), Maria-Louise Borg (Malta), Harry Seeverens (Netherlands), Stein Are Aksnes (Norway), Jacek Gralinski (Poland), Alexandre Diniz (Portugal), Ana Maria Vladareanu (Romania), Borut Peterlin (Slovenia), Frantisek Cisareik (Slovak Republic), Isabel Pena-Rey (Spain), Andor Wagner (Sweden) , Sabina Gallati (Switzerland), Edmund Jessop (UK)
EUCERD ECDC Representative: Andrew Amato
EUCERD Patient Organisation Representatives: Dorica Dan, Yann Le Cam, Christel Nourissier
EUCERD Pharmaceutical Industry Representatives: Wills Hughes-Wilson, Kevin William Loth, Samantha Parker, Barbara Valenta
EUCERD Rare Disease Projects under Health Programmes Representatives: Ségolène Aymé, Jean Donadieu, Dian Donnai, Laura Fregonese, Ester Garne, Domenica Taruscio, Joan Luis Vives Corrons, Thomas Wagner, Susan Webb
EUCERD Rare Diseases Research Projects under Framework Programmes for Research and Technological Development Representatives: Jean-Yves Blay, Kate Bushby, Marc de Baets, Olaf Hiort, Sophie Koutouzov, Gerard Wagemaker
EUCERD European Commission Participants: Catherine Berens, Jordi Llinares-Garcia (EMA), Georgios Margetidis, Antoni Montserrat Moliner, Stefan Schreck, Kerstin Westermark (EMA-COMP), Jaroslaw Waligora

Orphanet Partner Country Representatives: Tamara F. Sarkisian (Armenia), Hugh Dawkins (Australia) , Till Voigtlander (Austria), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann-Spangenberg (Germany), Helen Michelakakis (Greece), Sandor Janos (Hungary), Andrew Green (Ireland), Lina Basel (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbané (Lebanon), Viadutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequeiros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Ugur Ozbek (Turkey), Dian Donnai (UK)
For more information on the European Union Committee of Experts on Rare Diseases
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