29 February 2008 print
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Editorial
 

Oh Happy Day - Today marks the very First European Rare Disease Day!

 
29 February - Paris, France - If you are reading these words today, be aware that celebrations are unfolding all around you as the very first European Rare Disease Day becomes a reality. Across Europe and beyond, a bevy of conferences, media events, marches, and workshops are drawing awareness to the theme of today’s historical event: A Rare Day for Very Special People. Visit the European Rare Disease Day website to find out what’s going on near you.

Orphanet, the European portal for rare disease and orphan drug information, has had its sleeves rolled up for the last two years, working hard to contribute to the effort being made for rare disease patients across Europe. The revamped site, undergoing a rigorous final testing process, is scheduled to be officially unveiled in mid-March. The new website is a work of art – a customised portal providing a multitude of information and services all available from the site’s homepage. The database of rare diseases and orphan drugs has been enhanced with new information, including prevalence, onset, mode of inheritance and genetics. Links to related information sources, such as Swiss-Prot, Hugo or EuroGentest are just a click away. A major feature of the updated website is the addition of a classification scheme that categorises and cross-references any given disease by scientific, medical and genetic criteria. This new capability will help professionals and other users to access information from a generic category and has the added-value of improving data capture that can be instrumental in future policy making and fund distribution decisions as well as vital to treatment development in both the public and private sectors. The new site also improves searching for a rare disease by clinical sign or symptom. The orphan drug section has been enriched to provide information on the stage of development for any particular molecule from the moment it receives EMEA orphan designation until its market authorisation in Europe. The website also now provides access to the list of on-going clinical trials by molecule and to all orphan indications of a designated molecule - a service strongly requested by patients. Finally, navigation of the new site has been simplified to adequately guide first-time users – a growing part of the website’s visitors as the word of Orphanet spreads. The portal is fully accessible to visually and physically impaired users.


Orphanet is one of many organisations throughout Europe dedicated to improving conditions for rare disease patients and their families. OrphaNews Europe takes the occasion on this special day to acknowledge the efforts of all the various information services, research projects, patient associations, networks of excellence, industry initiatives and government actions - each working hard in its own way to ultimately make life better for rare disease patients and their families. Together we can.

 


 
Spotlight on...
 
Interview
 
Resuscitating a dream:
An anaesthesiologist strives to improve access to rare disease information

 
Uta Emmig first considered the problem of accessing information for rare disease anaesthetics when she was a graduate student. Now a working anaesthesiologist, she is reviving her earlier pursuit of improving information for working with rare disease patients in her particular field.

Uta Emmig, a German anaesthesiologist who specialised at the University Hospital of Aachen and is now working in Italy, knows from firsthand experience that anaesthesiology information specific to rare disease patients can be hard to come by. She has spent many hours surfing the web for literature providing concrete information on administering anaesthetics or the necessity for specialised equipment specific to rare disease patients. Even when such information exists in the literature (via case reports, for example) if the hospital or institution does not have access to a particular journal, the information remains inaccessible.

It is one thing for an anaesthesiologist to know in advance that they will be working with a specific patient with a rare condition that will require special monitoring or equipment, but what about the emergency room professional who encounters a patient with a disease they know little or nothing about? To address this vital need, Dr. Emmig is working to improve the information available to professionals in her field. OrphaNews Europe met with Dr. Emmig recently and was able to learn more about this critical aspect of rare disease patient management:


OrphaNews Europe: How did you first become aware of the need for information for anaesthesiologists working with rare disease patients?

Dr. Uta Emmig: I have been studying the anaesthesiology information resources relevant to rare diseases since 1996. My thesis advisor (Pr. Manfred Abel, former professor of paediatric anaesthesia at the university hospital of Cologne, currently head of the anaesthesia department in a teaching hospital in Cologne-Porz) first drew my attention to this problem. He actually created an electronic database with anaesthesia-relevant information for paediatric rare diseases with the goal of offering a counselling service for professionals in the 1990s. Unfortunately, he had to abandon his efforts due to lack of funding and partners. For my thesis, I conducted a study of the literature as well as a survey amongst my colleagues. The outstanding result was that it was very difficult to find information.

OrphaNews Europe: What kind of information do anaesthesiologists need to work optimally with this category of patients?

Dr. Uta Emmig:
For elective interventions/planned surgery:
1. Before the anaesthesia: “Do I have to perform other examinations?”
2. During the anaesthesia: “Do I have to monitor/control organ functions that I usually wouldn’t control?”
3. After the anaesthesia: “Do I have to keep a watch on the patient for a longer period than usual? Do I have to monitor other organ systems, e.g. blood glucose level.

For emergency surgery:
1. “Can I get rapid access to information on a specific rare disease?”
2. “How can I know which possible medications a patient might be taking and access detailed information concerning interactions with anaesthetic agents?”
3. “Does the hospital or clinic where I am working have specialised equipment available if necessary? If not, where can I access such equipment?”
Read the full interview with Dr. Uta Emmig
Contact Uta Emmig

 


 
EU Policy News
 
EMEA
 
EMEA implements electronic-only submission procedure
 
The European Medicines Agency (EMEA) has announced plans to implement an electronic-only submission procedure for information supporting marketing authorisation applications, leading ultimately to implementation of the Electronic Common Technical Document (eCTD) as the preferred format for electronic submissions. The change in procedures is expected to streamline application processing. Using the eCTD format in particular will permit standardisation and harmonisation and will facilitate navigation and lifecycle management capabilities. Thus, from 1 July, 2008, the EMEA will accept electronic-only submissions with no additional requirements for paper copies. From 1 January 2009, the EMEA will strongly recommend electronic-only submissions. From 1 July 2009, the EMEA will strongly recommend eCTD format electronic-only submissions. Read the question and answer document on electronic-only submissions.
 
A small but useful addition to the EMEA assessment report listing
 
Anyone visiting the European Medicines Agency A-Z listing of European Public Assessment Reports (EPARs) webpage might have noticed a new feature. Orphan designated products now have a small orange “O” icon next to their listing. Clicking on the “O” leads the reader to an information page on orphan medicines. EPARs provide a summary of the grounds on which the opinion was formed in favour of granting a marketing authorisation for a specific medicinal product.
 


 
National & International Policy Developments
 
Poland considers developing national rare disease programme
 
At the first meeting of the newly-elected Commission of Systemic Diseases, a working group of Poland’s paediatric scientific committee (the Committee of Human Development), working within the framework of the independent government-funded research organisation the Polish Academy of Sciences, it was decided to focus on rare disease issues, including the possibility of developing a national rare disease programme for Poland. Thus, rare diseases are to be included in the Committee of Human Development working programme for the coming four-year period. A first action toward this goal is the appointment of an Orphanet Advisory Board to the Committee in cooperation with the Polish Paediatric Society.
 
Luxembourg enlarges its neonatal screening programme
 
Luxembourg first implemented a neonatal screening programme in 1968. Testing currently includes three rare disorders: phenylketonuria (since 1968); congenital hypothyroidism (since 1978); and congenital adrenal hyperplasia, (since 2001). Over the past twenty years, some 100,000 infants have been tested, 42 of whom were diagnosed with one of these three disorders. Early diagnosis and treatment are vital for a positive outcome for these illnesses. Now Luxembourg is adding to its repertoire. As of 1 January, Luxembourg has broadened its newborn screening programme to include medium chain acyl CoA dehydrogenase deficiency (MCAD), an autosomal recessive disorder characterised by acute episodes of hypoketotic hypoglycemia with hepatomegaly (pseudo Reye syndrome), triggered by fasting or infections. As with the other rare diseases that have screening, early detection permits adapted therapeutic intervention before serious and permanent damage occurs.
 
Other European news
 
East meets West to discuss rare disease patient needs
 
On 7 December, stakeholders from throughout Europe gathered in the charming old-world convent of Cenankel in Soesterberg, the Netherlands for a workshop organised by the Dutch Steering Committee on Orphan Drugs. The meeting sought to facilitate the exchange of information concerning the diversity of rare disease and orphan drug resources within Europe. Participants from Eastern and Central European countries were especially encouraged to share their experience and knowledge. Twelve different countries were represented at the event: Bulgaria, Czech Republic, Estonia, Finland, Hungary, Israel, Italy, Malta, the Netherlands, Romania, Slovakia, and the United Kingdom. Three keynote speakers were invited to discuss European-level collaboration in the areas of regulatory affairs, public health care, and research:

Regulatory affairs Dr. Dagmar Stará (State Institute for Drug Control, Bratislava) described her experience of Dutch–Slovak cooperation in the area of medicinal product regulation. Collaboration enhanced the implementation of new European guidelines at the Slovak Institute of Drug Control.

Public health care Dr. Wienke Boerma (Netherlands Institute for Health Service Research) has worked on many European projects. He shared his experience of the introduction of primary health care concepts to Eastern and Central European countries, where efforts are being made to improve funds for research and healthcare, re-structure health insurance systems, develop new equipment, and train doctors and nurses in order to reduce hospitalisation. This experience yielded information concerning health care indicators and why differences still exist.

Science and patient driven research Dr. Evelyn Schaafsma works for the Science Shop (Pharmacy) in Groningen, the Netherlands. She illustrated the different possibilities and added-value of Science Shops - demand-driven independent research units located at different universities and faculties. There are Science Shops (established or still in formation) in many countries, including Czech Republic, Denmark, England, Estonia, France, Germany, Latvia, Portugal and Romania. These shops conduct mostly patient-oriented research.


These examples reiterated that communication between stakeholders working on similar issues in different countries is one of the most important assets available. Yet identifying colleagues and understanding different perspectives takes time. In the three examples presented, collaboration was ongoing for at least 10 years, often because positive results led to a project being followed by a new collaboration. Exchanging experience, stimulating awareness and gaining new skills can be formalised by conferences, workshops and training. In the three examples presented, start-up funds were available (from MATRA or Era-net).

In the afternoon, participants split into small subgroups, according to the topic on which they wanted to focus (drug development, healthcare expertise, or patient-driven research). Four questions helped guide discussion: How can players collaborate to move forward on the different topics? What are the experiences on this topic throughout Europe and by country? What are possible pitfalls and bottlenecks? What really works (best practices)? Results were noted down and shared with the participants.

Some conclusions
In many EU countries, the discrimination of minorities (including handicapped citizens and rare disease patients) is a big problem, on a parallel with unequal access to treatment. Change takes time. It is an obligation for those involved in rare diseases to bring into the limelight the specific needs of patients with a rare disease. In many countries, there is a delay of several years before a correct diagnosis is determined. Without diagnosis, there is generally no treatment or care. Another problem is the lack of information and the shortage of reliable data (prevalence data, for example). Finally, small countries have a lack of expertise for some rare diseases, requiring patients or experts to travel.

Working together, stakeholders can create a powerful instrument. Patients, doctors, researchers, and the pharmaceutical industry can all facilitate communication to insurance providers, health care professionals, politicians and government agencies. Yet in some countries, this bottom-up approach doesn’t work. Rather, key people in government have been convinced to act to improve the situation for rare disease patients. These countries work more from a top down approach to health care for rare diseases. In countries where there are strong and well organised patient organisations, rare disease patients have earlier access to treatment and care. But small groups stand stronger when they combine their forces in umbrella patient organisations, either nationally or pan-European. In small countries (such as Malta and the Netherlands) more orphan drugs are reimbursed. More active screening (such as cascade screening for genetic diseases) helps to diagnose (and treat) more people with a rare diseases.

One of the clearest conclusions is that great differences between European countries still exist. More pan-European awareness is needed. The European Commission Communication on European Action in the Field of Rare Diseases can help inform different European governments of important issues, such as the need for accurate diagnosis, registries, expertise centres, professional and medical student education, and the need for a research budget dedicated to rare diseases and orphan drugs. It is unnerving to note that not all European rare disease patients for whom an orphan drug is on the market are treated. Delays throughout the EU can be enormous. Differences exist from one country to another and also within certain countries (regional). The East Meets West workshop underscored that access to care and treatment remains one of the most important issues for rare disease patients.

 
French researcher wins international haematology prize
 
The prestigious William Dameshek prize, considered the highest award in the field of haematology, was awarded to Dr. William Vainchenker for his research on genetic mutations as activators of myeloproliferative diseases. In 2005, Dr. Vainchenker and his team identified a mutation responsible for polycythamia vera. This discovery has already changed the diagnosis and treatment of the disease and presents possible new therapeutic targets. Dr. Vainchenker is a director at the French national institute of medical scientific research (INSERM) and is based at the Gustave Roussy Oncology Institute. The American Society of Hematology awards the William Dameshek prize to significant contributions toward the understanding of blood-related diseases.
 
Other International News
 
The international genodermatoses project continues its work for Mediterranean-based patients
 
Genodermatoses are a group encompassing some 300 various genetic skin diseases, almost all of which are rare. The burden of severe genodermatoses is huge for patients and their family. Social exclusion, disability, and shortened life expectancy make this population very vulnerable. Prevalence is considered higher in the Mediterranean basin region due to a number of factors: consanguineous marital practices in certain regions, isolated cultural or religious sects, resistance to prenatal screening, and limited access to public resources. In 2003, the Fondation Rene Touraine (a European foundation promoting therapeutic advances in dermatology) and the Laboratoire Pierre Fabré launched an initiative entitled Genodermatoses and Mediterranean with the collaboration of specialists, scientists, policy makers and health officials from Euro Mediterranean and Middle Eastern countries. This initiative seeks to improve health care and social support, promote clinical research programmes, and foster networking in the field of severe genodermatoses. Each year, a Working Session is organised to bring together the project partners. In 2007, the Working Session was held in Alexandria, Egypt in late April. Eleven countries participated in the 2007 Working Session, in addition to three new countries that joined the initiative: Cyprus, Turkey and Saudi Arabia. Some achievements from the 2007 Working Session include involvement of new partners within many countries (geneticists, dermatologists, paediatricians, patient organisations, university clinics, et cetera); the finalisation of co-funding proposals at the European Union level in the fields of research and public health; specific social and healthcare training in various countries; the establishment of five working groups targeting diseases with a severe repercussion on quality of life: epidermolysis bullosa, severe ichthyosis, palmoplantar kerotoderma, xeroderma pigmentosum, and other severe genodermatoses (a subgroup of eight other identified diseases); new referral centres in four different countries; the integration of genodermatoses into major health policies in various countries (rare diseases in Algeria; skin diseases in Morocco; handicap in Egypt and Tunisia; genetic diseases in France); and various research initiatives in different countries. The goals for 2007-2008 have been identified as the establishment of good practices, health care community networks, access to drugs and medical devices. The 2008 Working Session will be held in Rabat, Morocco, from 6-7 June.
 
New UN publication focuses on disability issues
 
Disability is an international health and social concern whose prevalence is hard to capture. It is well known, however, that a large number of rare disease patients suffer from mental and/or physical disabilities. The Economic and Social Affairs department of the United Nations has recently created a newsletter designed to keep readers up to date on initiatives to increase inclusion in work, school and social activities amongst this segment of the population around the world. The newsletter, Enable, also features new publications and upcoming events relevant to the topic of disability.
 


 
Orphanet News
 
New Texts
 
New Orphanet Journal of Rare Diseases publications
 
Multiple osteochondromas
Monosomy 18p
Primary intestinal lymphangiectasia (Waldmann's disease)
Syndromic (phenotypic) diarrhea in early infancy
Smith–Lemli–Opitz syndrome: pathogenesis, diagnosis and management (published in the European Journal of Human Genetics, in association with Orphanet)

 


 
New Syndromes
 
22q11.2 distal deletion: a new phenotype distinct from DiGeorge syndrome and velocardiofacial syndrome
 
Microdeletions within chromosome 22q11 have been linked to two syndromes: DiGeorge syndrome and velocardiofacial syndrome. The authors of this study have identified six patients with a 22q11.2 distal deletion presenting a distinct phenotype. All have distinct facial dysmorphia perhaps linked to prematurity, pre-or post-natal growth delays, developmental delays and skeletal anomalies. Two patients also have cardiovascular malformations and a third has a cleft palate.
Read the PubMed abstract

 
Am J Hum Genetics ; 214-221 ; January 2008
 
Microtia, eye coloboma, and imperforation of the nasolacrimal duct: a new autosomal dominant syndrome
 
A Belgian team describes a family afflicted with an autosomal dominant syndrome characterised by microtia, eye coloboma, and imperforation of the nasolacrimal duct. This phenotype is linked to five tandem copies of a copy-number-variable region of chromosome 4p16. This is the first example of an amplified copy number variant associated with a Mendelian disorder.
Read the PubMed abstract

 
Am J Hum Genetics ; 181-187 ; January 2008
 
A new retinopathy linked to BEST1 biallelic mutations
 
The authors describe five families with a distinct retinal disorder, autosomal-recessive bestrophinopathy that is consequent upon biallelic mutation in BEST1 and is associated with central visual loss, a characteristic retinopathy, an absent electro-oculogram light rise, and a reduced electroretinogram. Heterozygous mutations in BEST1 have previously been found to cause the two dominantly inherited disorders, Best macular dystrophy and autosomal-dominant vitreoretinochoroidopathy.
Read the PubMed abstract

 
Am J Hum Genetics ; 19-31 ; January 2008
 
SERKAL syndrome: female to male sex reversal and renal, adrenal, and lung dysgenesis
 
The authors describe three foetus with a lethal autosomal recessive syndrome characterised by SEex reversal and Kidney, Adrenal and Lung dysgenesis. They identified a disease-causing homozygous missense mutation in the human WNT4 gene.
Read the PubMed abstract

 
Am J Hum Genetics ; 39-47 ; January 2008
 


 
New Genes
 
Familial erythrocytosis: hypoxia-inducible factor alpha 2 is at cause
 
Familial erythrocytosis is a primary polycythaemia characterised by an increase of haematocrit and haemoglobin levels. Hypoxia-inducible factor (HIF) alpha, which has three isoforms, is central to the continuous balancing of the supply and demand of oxygen throughout the body. The authors describe a family with erythrocytosis and a mutation in the HIF2A gene, which encodes the HIF-2alpha protein. Their functional studies indicate that this mutation leads to stabilisation of the HIF-2alpha protein and suggest that wild-type HIF-2alpha regulates erythropoietin production in adults. HIF-alpha is a transcription factor that modulates a wide range of processes, including erythropoiesis, angiogenesis, and cellular metabolism.
Read the PubMed abstract

 
NEJM ; 162-168 ; January 2008
 
Lethal multiple pterygium syndrome has severe rapsyn function loss
 
Lethal multiple pterygium syndrome (MPS) is characterised by intrauterine growth delay, pterygia present in multiple areas (chin to sternum, cervical, axillary, humero-ulnar, crural, popliteal, and the ankles) and flexion contractures giving rise to severe arthrogryposis. Ressive mutations in the embryonal acetylcholine receptor g subunit (CHRNG) can cause both lethal and nonlethal MPS. The authors have identified a new homozygous mutation in the gene encoding raspyn. Mutations in this gene have previously been identified in patients with congenital myasthenia. Whereas incomplete loss of rapsyn function may cause congenital myasthenia, more severe loss of function can result in a lethal foetal akinesia phenotype.
Read the PubMed abstract

 
Am J Hum Genetics ; 222-227 ; January 2008
 
Autosomal-dominant snowflake vitreoretinal degeneration is caused by a retinal potassium channel gene mutation
 
Autosomal-dominant snowflake vitreoretinal degeneration is a progressive ocular disease affecting multiple tissues within the eye and characterised by fibrillar degeneration of the vitreous humor, early-onset cataract, minute crystalline deposits in the neurosensory retina, and retinal detachment. The authors have identified heterozygous mutations in gene KCNJ13, encoding a potassium channel localized to human retina and retinal pigment epithelium.
Read the PubMed abstract

 
Am J Hum Genetics ; 174-180 ; January 2008
 
X-linked infantile spinal muscular atrophy linked to defects in the ubiquitin-proteasome pathway
 
X-linked infantile spinal muscular atrophy (XL-SMA) is an X-linked disorder presenting with hypotonia, areflexia, and multiple congenital contractures (arthrogryposis) associated with loss of anterior horn cells and infantile death. The authors have identified missense mutations in UBE1 gene in two families and a synonymous substitution in three other families. In the case of the latter, gene expression is reduced and alters the methylation pattern of exon 15, implying a plausible role of this DNA element in developmental UBE1 expression in humans.
Read the PubMed abstract

 
Am J Hum Genetics ; 188-193 ; January 2008
 
Autosomal-recessive nonsyndromic hearing impairment: ESRRB gene may have mutations
 
Autosomal recessive nonsyndromic hearing impairments are a heterogeneous group of genetic disorders for which 67 loci, called DFNB, and 24 genes have been identified. In a Turkish consanguineous family, the authors identified locus DFNB35 and identified a homozygote duplication of seven base pairs in gene ESRRB. They confirmed the presence of mutations in this gene in four other families of whom the hearing impairment had already been linked to the same locus. ESRRB encodes an estrogen-related receptor protein. In mice, the orthologue protein is expressed during inner-ear development and is present postnatally in the cochlea.
Read the PubMed abstract

 
Am J Hum Genetics ; 125-138 ; January 2008
 
Familial primary localised cutaneous amyloidosis has oncostatin M receptor-beta mutations
 
Familial primary localised cutaneous amyloidosis is an autosomal dominant disease characterised by chronic skin itching and deposition of epidermal keratin filament-associated amyloid material in the dermis. In three families, the authors identified mutations in gene OSMR, encoding oncostatin M-specific receptor beta, which is a component of two receptors: oncostatin M and interleukin 31, implicated in keratinocyte proliferation, differentiation, apoptosis, and inflammation.
Read the PubMed abstract

 
Am J Hum Genetics ; 73-80 ; January 2008
 
Mitochondrial complex I: C6ORF66 is an assembly factor
 
The authors performed homozygosity mapping in five patients from a consanguineous family who presented with infantile mitochondrial encephalomyopathy attributed to a deficit of respiratory chain complex I. They identified a mutation in gene C6ORF66. Their research suggests that the gene encodes a respiratory chain complex I assembly factor.
Read the PubMed abstract

 
Am J Hum Genetics ; 32-38 ; January 2008
 
X-linked scapulo-axio-peroneal myopathy: FHL1 mutated in three families
 
Two articles published in the American Journal of Human Genetics describe the identification of mutations in gene FHL1 in patients with X-linked scapulo-axio-peroneal myopathy. The patients studied present a particular phenotype of scapulo-peroneal weakness, pseudoathleticism or hypertrophy, and bent-spine syndrome. The gene FHL1 is highly expressed in skeletal muscle and may contribute to stability of sarcomeres and sarcolemma, myofibrillary assembly, and transcriptional regulation.
Read the first PubMed abstract
Read the second PubMed abstract

 
Am J Hum Genetics ; 88-99 ; January 2008
Am J Hum Genetics ; 208-213 ; January 2008
 


 
Research in Action
 
Fundamental Research
 
5q- myelodysplastic syndrome: identification of a causative gene via RNA interference screening
 
5q- syndrome is a subtype of myelodysplastic syndrome characterised by a defect in erythroid differentiation. The causative gene has not been identified to date. The authors describe an RNA-mediated interference (RNAi)-based approach to discovery of the 5q- disease gene in the normal haematopoietic progenitor cells. They observed that a partial loss of ribosomal protein RPS14 sufficed to mimic the phenotype seen in patients. This type of approach presents a strategy to identify gene dosage anomalies at the origin of diseases.
Read the PubMed abstract

 
Nature ; 335-339 ; January 2008
 
Clinical Research
 
Hemochromatosis: More men with C282Y homozygote mutation develop iron-overload related disease than their female counterparts
 
Hemochromatosis is a genetic disease characterised by an iron overload due to digestive hyperabsorption. It is caused by HFE gene mutations, of which allele C282Y is most frequently seen in patients. The authors demonstrate that C282Y homozygote men have a higher risk than women with the same genotype to develop a disease linked to iron overload (28.4% of men versus 1.2% of women).
Read the PubMed abstract

 
NEJM ; 221-230 ; January 2008
 
Dysequilibrium syndrome: VLDLR gene may be the only one affected
 
Dysequilibrium syndrome is characterised by intellectual deficit, equilibrium and locomotive problems, strabismus and small stature. A homozygous deletion in the short arm region of chromosome 9, including two genes expressed in the brain, have previously been linked to this syndrome. In this study, the authors have identified a homozygous mutation that affects just one of these genes: VLDLR, encoding a very weak density lipoprotein receptor implicated in neuroblast migration in the cerebral cortex and the cerebellum.
Read the PubMed abstract

 
Eur J Hum Genetics ; 270-273 ; February 2008
 
Hypomyelination and juvenile onset cataract: cataracts are not always present at birth
 
DRCTNNB1A gene mutations are responsible for an autosomal recessive disease associating hypomyelination and congenital cataracts. The authors have identified an intragenic deletion in this gene in a family presenting juvenile onset cataract, thus broadening the phenotype for this disease. Congenital cataract is thus not an essential criterion for differential diagnosis.
Read the PubMed abstract

 
Eur J Hum Genetics ; 261-264 ; February 2008
 
Spinocerebellar ataxia type 17: repeat configuration is a critical determinant for instability
 
Patients with spinocerebellar ataxia type 17 present ataxia, pyramidal and extrapyramidal signs, learning difficulties, pyschosis and epileptic crises. This ataxia is due to expanded CAG nucleotide repetitions in gene TBM. The repetitions may be either continuous or interrupted. The authors observed that for a given stretch of repetitions, the instability of mutated alleles is two or three times higher when the repetitions are continuous. This information confirms the hypothesis that repetition configuration is a determinant of instability.
Read the PubMed abstract

 
Eur J Hum Genetics ; 215-222 ; February 2008
 
Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity
 
Auriculo-condylar syndrome, an autosomal dominant disorder of first and second pharyngeal arches, is characterized by malformed ears ('question mark ears'), prominent cheeks, microstomia, abnormal temporomandibular joint, and mandibular condyle hypoplasia. The authors have linked the transmission of the disease to chromosome region 1p21.1-q23.3 in a Brazilian family. However, in a second family no link could be established, demonstrating the genetic heterogeneity of the disease.
Read the PubMed abstract

 
Eur J Hum Genetics ; 145-152 ; February 2008
 
Aicardi syndrome: incidence is around 1 in 100,000
 
Aicardi syndrome is a developmental disorder characterised by agenesis of the corpus callosum, retinal anomalies, seizures and developmental delay. It is transmitted as an X-linked disorder with presumed lethality in males. Using data from 408 patients gathered from different international sources, the authors calculate incidence to be 1 in 105,000 live births in the US and 1 in 93,000 live births in the Netherlands. The risk of mortality peaks at age 16 and the probability of survival at age 27 is 0.62.
Read the PubMed abstract

 
J Child Neurol ; Epub ahead of print ; January 2008
 
Autism: Two new susceptibility genes from the neurexin superfamily have been identified
 
Three independent studies published in « The American Journal of Human Genetics »have identified a new susceptibility gene for autism: CNTNAP2. This gene encodes a neurexin family protein and is expressed in areas of the brain instrumental to language development. A second gene, NRXN1, encoding neurexin 1, was identified in a fourth study published in the same journal.
Read the first PubMed abstract
Read the second PubMed abstract
Read the third PubMed abstract
Read the fourth PubMed abstract

 
Am J Hum Genetics ; 150-159 ; January 2008
Am J Hum Genetics ; 160-164 ; January 2008
Am J Hum Genetics ; 165-173 ; January 2008
Am J Hum Genetics ; 199-207 ; January 2008

 
Gene Therapy
 
Congenital erythropoietic porphyria: complete phenotype correction by gene therapy in mice
 
Congenital erythropoietic porphyria is a severe autosomal-recessive disorder characterised by a deficiency in uroporphyrinogen III synthase, the fourth enzyme of the heme biosynthetic pathway. The authors used a murine model to check the feasibility of hematopoietic stem cell gene therapy in this disease. They succeeded in achieving complete and long-term enzymatic, metabolic, and phenotypic correction of the disease.
Read the PubMed abstract

 
Am J Hum Genetics ; 113-124 ; January 2008
 
Diagnostic Approaches
 
Sézary syndrome: CD158K/KIR3DL2 is a differential diagnostic marker in patients with erythroderma
 
The distinction between Sézary syndrome and benign erythrodermic inflammatory diseases is difficult to make both clinically and on skin biopsies, since histomorphology can provide nonspecific results. The authors identified a marker specific to Sézary syndrome: CD158K/KIR3DL2. Using conventional and/or quantitative real-time reverse transcription (RT)-PCR analysis of skin biopsies allowed for distinction between Sézary syndrome and benign erythrodermic inflammatory disease.
Read the PubMed abstract

 
J Invest Dermatol ; 465-472 ; February 2008
 


 
Patient Management and Therapy
 
Advanced-stage mantle cell lymphoma: a new prognostic index
 
There is no generally established prognostic index for patients with mantle cell lymphoma (MCL) because the International Prognostic Index (IPI) and Follicular Lymphoma International Prognostic Index (FLIPI) have been developed for diffuse large cell and follicular lymphoma patients, respectively. Using data of 455 advanced stage MCL patients treated within 3 clinical trials, the authors examined the prognostic relevance of IPI and FLIPI and derived a new prognostic index (MCL international prognostic index, MIPI) of overall survival. According to the MIPI, patients were classified into low risk (44% of patients, median OS not reached), intermediate risk (35%, 51 months), and high risk groups (21%, 29 months), based on the 4 independent prognostic factors: age, performance status, lactate dehydrogenase (LDH), and leukocyte count. Cell proliferation was exploratively analyzed as an important biologic marker and showed strong additional prognostic relevance. The MIPI is the first prognostic index particularly suited for MCL patients and may serve as a tool to facilitate risk-adapted treatment decisions in patients with advanced stage MCL.
Read the PubMed abstract

 
Blood ; 558-565 ; January 2008
 
Systemic Lupus Erytematosus: new treatment recommendations
 
EULAR, The European League Against Rheumatism has developed a new series of recommendations for the management of Systemic Lupus Erytematosus, an auto-immune disease characterised by the presence of anti-nuclear auto-antibodies. Read the recommendations
 
Ann Rheum Dis ; 195-205 ; February 2008
 


 
Orphan Drugs
 
Nine EMEA orphan drug designations for February
 

The COMP (Committee for Orphan Medicinal Products) adopted the following nine positive opinions on orphan medicinal product designation at its February meeting for the treatment of:

- retinitis pigmentosa
- Wilson disease
- small cell lung cancer
- Charcot-Marie-Tooth disease type 1A
- spina bifida
- pancreatic cancer
- amyotrophic lateral sclerosis
- ovarian cancer
- idiopathic pulmonary fibrosis
Consult the European Registry for Orphan designations
Consult the Orphanet list of orphan drugs authorised for marketing in Europe

 


 
Grants
 
Call for proposals: European research projects on neurodegenerative diseases
 
ERA-NET Neuron has issued a call for proposals for European research projects on neurodegenerative diseases of the central nervous system. The deadline for proposal submission is 07 April, 2008.
For further information.

 


 
News from the Patients' Associations
 
An orphan disease review in Algeria
 
The Algerian Williams and Beuren Syndromes Association, founded in 2002 by parents of an afflicted child, has created a review dedicated to raising awareness for rare diseases in Algeria. The first issue of Maladies Orphelines provides basic information on an array of diseases, including a feature article on a little girl with Rothmund Thomsan syndrome, and also contains sections on psychology, social services, and patient testimonies. Five thousand copies of the first issue of the French-language review have been distributed, and an on-line version is in preparation. The review is scheduled to appear twice yearly.
 


 
What's on Where?
 
Rare Diseases: Channels and Transporters
 
Date: 8-12 March 2008
Venue: Sant Feliu de Guixols, Spain

The conference is devoted to channels and transporters involved in rare inherited diseases. Specifically TRP and CLC channels, connexins, mitochondrial transporters, heteromeric amino acid transporters, neurotransmitter transporters, ABC transporters and related diseases will be covered.
For further details

 
Second European Symposium on Rare Anaemias
 
Date: 13-14 March 2008
Venue: Nicosia, Cyprus

Sessions include current progress in prenatal and neonatal diagnosis of haemoglobinopathies, iron overload and chelation therapy, very rare anaemias, treatment of haemoglobinopathies, and red blood cell hereditary disorders.
For further details

 
Beyond Medicine: Providing Quality Genetic Testing Service for the Public in the World
 
Date: 16 March 2008
Venue: Tokyo, Japan

The purpose of the symposium is to exchange experiences and opinions on various issues relating to the provision of quality genetic testing services, such as information provided to consumers, regulatory schemes and genetic counseling.
For further details

 
Genomic Disorders 2008
 
Date: 17-20 March 2008
Venue: Cambridgeshire, UK

Topics to be discussed will include copy number variation and assays, structural variation predisposing to genomic rearrangement, mechanisms underlying genomic disorders, genomic rearrangements in common diseases and genetic syndromes, model organisms in the study of genomic disorders and potential therapeutic approaches.

For further details

 
Fifth International Congress on FMF and Systemic Autoinflammatory Diseases
 
Date: 4-8 April 2008
Venue: Rome, Italy

This conference will review current knowledge of the mechanisms of innate immunity and their relevance to the pathogenesis of autoinflammatory and other chronic diseases.
For further details

 
19th Conference of the German Society of Human Genetics
 
Date: 8-10 April 2008
Venue: Hannover, Germany

This year the main focus will be on the following subjects: Genetic origins of pain intensity, connective tissue disorders and complex infectious diseases; New therapeutic approaches to genetic diseases; The role of miRNAs and epigenetic modification; Proteomics; The structure of human genetic health care services in Europe.
For further details

 
International Ataxia-Telangiectasia Workshop 2008
 
Date: 22-26 April 2008
Venue: Kyoto, Japan

Topics include the roles of ATM and its related proteins in the DNA damage responses and in the tumorigenesis. The biological roles of ATM in the development of immune system, nervous system, and the stem cell systems are another essential area towards new therapies for A-T.
For further details

 
Second International Workshop on Minicircle-DNA
 
Date: 7-9 May 2008
Venue: Bielefeld, Germany

Following on the success of the 2007 conference, and focusing on technology and IP and application.
For further details

 
ICORD 4th International Conference on Rare Diseases and Orphan Drugs
 
Date: 20-22 May 2008
Venue: Washington, DC US
For further details

 
13th International Conference for Behçet's Disease and 5th Patients' Convention
 
Date: 24-27 May 2008
Venue: Klagenfurt, Austria

With presentations and discussions on oral, eye, genital and skin involvement, as well as paediatric patients, drug trials and future perspectives.
For further details

 
Myology 2008: Treatments – The Turning Point
 
Date: 29 May - 1 June 2008
Venue: Marseilles, France

Focusing on the development of therapies and the setting up of trials on humans for rare diseases in the field of myology.
For further details

 
First Conference on Translational Research in Paediatric Rheumatology
 
Date: 29 May - 1 June 2008
Venue: Genoa, Italy

Using the field of rare paediatric rheumatic disorders as a paradigm, Anticipating Changes in Drug Development for Children: Building on Paediatric Rheumatology will examine the medicine research and development process, from pre-clinical and early-phase clinical development, to biomarker validation, study design and management, data analysis, ethical review, regulatory submission and research governance. The conference is meant to further stimulate interaction among the three major stakeholders in the drug development process, namely, academia, industry and regulatory authorities.
For further details

 
5th International Congress of Rehabilitation in the Field of Neuromuscular Disorders
 
Date: 30 May – 1 June 2008
Venue: Marseilles, France

With sessions on gene-based therapies, patient evaluation, pain and fatigue management, and treatment options.
For further details

 
EuroGentest Genetic Testing Accreditation and Quality Assurance Programmes
 
Date: 30-31 May 2008
Venue: Barcelona, Spain

EuroGentest presents two workshops and a round table session on the topics of accreditation in genetic testing labs, quality assurance and managing the human side of change.
For further details

 
40th European Human Genetics Conference
 
Date: 31 May-3 June 2008
Venue: Barcelona, Spain

In conjunction with the European Meeting on Psychosocial Aspects of Genetics 2008. Progamme will cover the latest developments in the field of human genetics that are of interest both for clinicians and research scientists.
For further details

 
14th International Conference on Prenatal Diagnosis and Therapy
 
Date: 1-4 June 2008
Venue: Vancouver, Canada

Conference sessions will include foetal imaging, cytogenetics, foetal DNA/RNA, PGD, screening, teratology, and legal aspects of prenatal diagnostics and therapy. The deadline to submit an abstract for this conference is 4 February 2008.
For further details

 
5th International Cystinosis Conference
 
Date: 27-28 June 2008
Venue: Dublin, Ireland

World experts in the field of Cystinosis will attend and the latest research in this very rare disease will be presented. The event is unique as it combines a high-level scientific and medical conference as well as being a family and patient friendly conference. Deadline for abstracts: 11 April 2008.
For further details

 
Fourth International Neuroacanthocytosis Symposium: Bridging Clinical and Basic Aspects
 
Date: 1-2 July 2008
Venue: Oxford and London, England

Including clinical aspects of chorea acanthocytosis and McLeod syndrome, muscle and nerve neuropathology and syndromes related to NA.
For further details

 
Genetic Alliance Annual Conference 2008
 
Date: 11-13 July 2008
Venue: Bethesda, MD, US

Brings advocates, health professionals, policy makers, industry representatives, researchers, and community leaders together for workshops and discussions.
For further details

 
Fourth International Conference on Metals and Genetics
 
Date: 21-24 July 2008
Venue: Paris, France

The main topics will include metal-associated diseases: molecular and systemic biology approaches; characterisation and speciation of metal in proteins and biological tissues; and metals and environmental health implications.
For further details

 
Barth Syndrome: On Track Toward a Cure - 4th International Conference
 
Date: 21-26 July 2008
Venue: Florida, USA

This conference will be dedicated to increasing knowledge and accelerating advances in research for this rare metabolic genetic disorder. It will bring together basic scientists, clinical researchers, treating physicians, other professionals, and affected individuals and families to focus on the syndrome through a series of carefully organised sessions.
For further details

 
15th Paediatric Rheumatology European Society Congress
 
Date: 14-17 September 2008
Venue: University College London, UK

The programme will cover four main topics through keynote lectures, abstract presentations and educational workshops: juvenile arthritis, juvenile dermatomyositis, vasculitis and pain. There will be novel symposia such as sport and exercise in young people.
For further details

 
6th World Rett Syndrome Congress
 
Date: 10-13 October 2008
Venue: Paris, France

Various aspects of Rett syndrome and MECP2 functioning, including fundamental, clinical and management topics.
For further details

 
Tenth International Meeting on Osteogenesis Imperfecta
 
Date: 15-18 October 2008
Venue: Ghent, Belgium

Topics include: Bone homeostasis, murine models/collagen biology/biophysics, classification, genetics: genotype-phenotype, prenatal diagnosis/preimplantation diagnosis, biphosphonates, orthopedic management, hearing loss: physiopathology, surgery and imaging, other medical management issues, stomatology/dentistry, psychosocial aspects, new (therapeutic) perspectives.
For further details

 


 
Orphanews Europe, the newsletter of the Rare Diseases Task Force
Orphanews Europe is supported by the European Commission's DG SANCO
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Louise Taylor
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Editorial Board: Ségolène Aymé, Catherine Berens, Olaf Bodamer, Helen Dolk, Anders Fasth, Laura Fregonese, Benjamin Guesdon, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Charlotte Rodwell, Paloma Tejada, Aurélie Vandeputte
National Contact Point: Till Voigtländer (Austria), Jean Jacques Cassiman (Belgium), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), Andres Metspalu (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann (Germany), Michael Petersen (Greece), János Sándor (Hungary), Andrew Green (Ireland), Judith Melki (Israel), Bruno Dallapiccola and Domenica Taruscio (Italy), Andre Megarbane (Lebanon), Vaidutis Kucinskas (Lithuania), Alfred Cuschieri (Malta), Abdelaziz Sefiani (Morocco), Martina Cornel (Netherlands), Stein Are Aksnes (Norway), Jolanta Sykut-Cegielska (Poland), Jorge Sequeiros (Portugal), Dragica Radojkovic (Serbia), Ludovit Kadasi (Slovakia), Borut Peterlin (Slovenia), Miguel del Campo and Manuel Posada de la Paz (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Habiba Chaabouni-Bouhamed (Tunisia), Fatmahan Atalar and Ugur Ozbek (Turkey), Edmund Jessop and Idoia Gomez-Paramio (United Kingdom)
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