29 September 2010 print
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Editorial
 
A rare glimpse: French biomedicine agency report offers a view of the genetic testing activity in the country
 

The 2009 annual report of the French Agence de Biomédecine features for the first time data on the post-natal genetic testing activity performed in the country. Under French law, laboratories are obliged to report their activities to the watchdog agency. The data, collected via a partnership with rare disease information portal Orphanet, were for the first time subject to an electronic analysis. Data were culled from 239 laboratories, of which 75 perform cytogenetic testing, and 182 offer molecular genetic testing. Of this latter group, laboratories offer a range of between one and 78 tests, although over 30% limit their scope to just one or two tests.

The 2009 report shows that genetic testing activity is robust in the Hexagon (the epithet mainland France is frequently referred to due to its geographical shape), with over 270,000 molecular genetic analyses performed on 1042 of the 1143 genetic tests available in the country. These diagnostics concerned 951 different disorders – many of which are rare. These figures demonstrate that the molecular genetic test offer available in France must be maintained. Although just two indications – hemochromatosis and non-rare thrombophilia – represented more than 41% of analyses performed in 2009, the results illustrate that there was at least one demand for over 90% of the available tests. Other genetic tests performed in 2009 included over 6,400 pharmacogenetic analyses – a growing field of demand for genetic testing.

For cytogenetic testing, some 80,000 analyses were performed using caryotype (over 68,200) or FISH (12,000) techniques. Intellectual deficit, malformations, and developmental anomalies were amongst the indications. The new CGH array technology was used by both cytogenetic and molecular laboratories. Some 6,600 such tests were performed, most often (91% of cases) for intellectual deficit/malformations. A high level of unbalanced rearrangements was detected via this technique, probably a reflection of the fact that CGH arrays were performed in complement to a caryotype analysis.

Pre-natal testing activity in France
Besides post-natal testing activity, the annual report contains the data from prenatal diagnostics undertaken in 2008, with a comparison between the years 2006, 2007, and 2008. Over 80,000 foetus were subject to cytogenetic analysis in over 70 laboratories in 2008. Of these, almost 4,000 had a positive diagnosis. Maternal age, parental chromosomal anomalies, prior pregnancies with a chromosomal anomaly, and ultrasound-detected anomalies were amongst the most frequent indication for cytogenetic testing.

Of 3,147 foetus subject to molecular genetic testing in 2008, some 500 had positive diagnoses rendered. Cystic fibrosis, SMA, sickle cell anaemia, beta-thalassemia, X-linked disorders, and Rett syndrome were amongst the most frequent autosomal recessive conditions tested, while Steinert myotonic dystrophy, Charcot-Marie-Tooth disease, neurofibromatosis type 1 and Huntington disease were amongst the autosomal dominant conditions most frequently tested. Uniparental disomies (Prader-Willi/Angelman syndrome) were also tested in over 300 foetus. Overall, for the molecular genetic tests, 17% of foetus tested were affected. Between 50% and 90% of affected pregnancies were terminated, depending on the condition. Testing for these conditions was typically initiated due to an existing condition in the family or following an anomaly detected by ultrasound examination. 2009 saw the technology for pre-natal diagnostics advance, with the possibility to obtain an analysis combining nuchal translucency and a blood screen test before 12 weeks of pregnancy. For molecular genetic testing, technology now allows genotyping using the foetal DNA circulating in the maternal blood.

The annual report also includes data on cell, tissue and organ donations and transplantations, embryonic and stem cell research, and assisted reproductive activities.

The French Biomedicine Agency, a public organisation operating under the supervision of the Minister of Health, was created under the Bioethic Law of 2004. Its overriding function is to “guarantee equity, ethics, and transparency for the activities under its responsibility and for anticipated developments”.

Consult the 2009 annual report of the French Biomedicine Agency (in French language)
 


 
EU Policy News
 
Innovative Medicines Initiative experiencing growing pains
 
On 20 December 2007, the European Council adopted four Joint Technology Initiatives, including the public-private Innovative Medicine Initiative (IMI). Founded by the European Commission and the EFPIA (European Federation of Pharmaceutical Industries and Associations), the IMI joint undertaking is designed to support pre-competitive pharmaceutical research and development. Its goal is to deliver new approaches, methods and technologies for the drug development process, in order to accelerate the development of safe and more effective medicines for patients. Innovative medicines hold great promise for rare disease patients. However, almost three years down the road, academic researchers are expressing dissatisfaction with the initiative. In an open letter from the League of European Research Universities (LERU) addressing the IMI board, Member State representatives and the IMI IP working group, several points of contention are raised – primarily around the themes of financing and intellectual property rights. While expressing their desire to continue collaboration with industry via the IMI, the letter contains a laundry list of problems with the initiative. Following an article on the subject published in Nature in July, IMI leaders responded with a letter of their own (also appearing in Nature), justifying the IMI’s intellectual-property policies while acknowledging that there could be certain “bumps on the road” to innovation. It is hoped that these bumps will not hinder the development of innovative treatments for rare diseases.
Consult the LERU letter

 


 
National & International Policy Developments
 
UK government aims to disband Human Fertilisation and Embryology Authority
 
In the United Kingdom, the Human Fertilisation and Embryology Authority (HFEA) is the independent regulator for in vitro fertilisation treatment and embryo research. Established in 1991 as part of the Human Fertilisation and Embryology Act (1990), the HFEA also regulates the storage of gametes (eggs and sperm) and embryos. It is one of over 20 “Arm's Length Bodies” - ie, non-departmental public agencies accountable to the Department of Health. In a report published in July, the Department of Health unveiled its intention to disband the HFEA and certain other Arm's Length Bodies in a bid to cut costs. The functions of the HFEA are to be divvied up between “… a new research regulator, the Care Quality Commission and the Health and Social Care Information Centre.” In response to the report, the HFEA issued a press release stating: “IVF needs to be effectively regulated and the current system has served the public, patients and licensed centres well. Our task now is to deliver the organisational change that the Government has decided on and to ensure the continuity of the very high standard of regulation that the sector deserves and expects”. The Human Tissue Authority is also to be disbanded and its functions distributed amongst similar agencies as the HFEA. The deadline for dismantling the authorities is before the end of the current term of the Parliament – May 2015 at the latest.
Consult the HFEA press release
Consult the Department of Health press release

 
A new commissioning guide for inherited cardiovascular condition services
 
In July 2009, OrphaNews Europe reported on the Heart-to-Heart report, an in-depth needs assessment study of inherited cardiovascular conditions and the services available to treat them in the United Kingdom, produced by the independent non-profit Foundation for Genomics and Population Health (PHG Foundation). Following from this report, comes the Commissioning Guide: Services for Patients with Inherited Cardiovascular Conditions. Specific to the situation in the UK, the guide nonetheless identifies and discusses many of the general elements necessary to diagnosing and managing patients anywhere with inherited cardiovascular conditions –which include familial hypercholesterolaemia, the arrhythmia syndromes (long-QT syndrome, short-QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia); cardiomyopathies (caused mainly by mutations in the proteins making up the contractile system of the myofibrils), including hypertrophic and dilated cardiomyopathies; inherited arteriopathies which cause catastrophic rupture of the blood vessels (Marfan, Ehlers-Danlos, and Loeys-Dietz syndromes); and muscular dystrophies (Emery-Dreifuss muscular dystrophy and myotonic dystrophy). The guide divides this family of conditions into five categories, and identifies nine elements essential for providing a comprehensive service for these patients. These include key clinical issues in providing an effective service, treatment, genetic testing, prevention and family care. The components identified are applicable to any country designing comprehensive care for inherited heart conditions – almost all of which are rare. Consult the guide
 
A method to evaluate rare disease candidates for newborn screening programme
 
A paper published earlier this year in Genetics in Medicine describes the method for evaluating conditions for inclusion in the population-based newborn screening programme in the USA. The authors discuss the framework used in the USA, where over two dozen disorders are recommended for screening. According to the authors, amongst the data taken into consideration are “the accuracy and specificity of screening and diagnostic tests for nominated disorders, the extent of predicted health benefits, harms impact on disease course, and cost from early diagnosis and treatment”. With the rapid advances in technology for rare disease newborn screening, more candidates are cropping up for potential inclusion in newborn screening programmes. Consequently, there is a widening gulf between the newborn screening policies of different countries. Consult the abstract
 


 
Ethical, Legal & Social Issues
 
Levelling the playing field for genetic testing – how to implement standardised methods for controlling quality
 
Two articles appearing in the European Journal of Human Genetics discuss the framework for assuring standardised quality-controlled genetic testing. The first, open-access article, A Standardized Framework for the Validation and Verification of Clinical Molecular Genetic Tests discusses the basic principles for including validation and verification in the implementation process for human molecular genetic testing. The article provides a “practical guide for diagnostic molecular geneticists to aid them in designing, performing and reporting suitable validation or verification for the tests they wish to implement” and walks the reader through the implementation process. The paper discusses the different types of potential tests – various forms of quantitative, categorical (semi-quantitative) or qualitative testing – and provides specific validation and verification considerations for each type. The authors also discuss experimental design and results reporting.

The second paper, entitled, Approaches to Quality Management and Accreditation in a Genetic Testing Laboratory, discusses the growing international compliance with the International Organization for Standardization (ISO) 15189 for the accreditation of medical laboratories, as the “optimal approach to assuring quality in medical testing”. The authors list a number of recommendations and strategies for genetic laboratories to adopt in order to ascertain a reliable, standardised system for managing quality. Amongst the recommendations discussed are key aspects such as “document control, external quality assessment, internal quality control, internal audit, management review, validation, as well as managing the human side of change”. The article points the reader to the myriad of resources available via the Network of Excellence EuroGentest.
Consult A standardized framework for the validation and verification of clinical molecular genetic tests
Consult the PubMed abstract for the second article

 


 
Orphanet News
 
To each, his own ... Orphanet
 
Orphanet, the pan-European reference and information portal for rare diseases and orphan drugs with partners in 38 countries, has taken a step to customise further its offer. Each of the Orphanet partners is busy creating its own country site, available in its own language(s). These local sites will feature information on rare diseases and orphan drugs, as well as local political, medical and scientific news, and locally sponsored conferences and events. It is hoped that the sites will raise the visibility of the Orphanet teams working in each country. The central Orphanet database of diseases and resources, available in five European languages, can be easily accessed via the local sites. Thus far, France, Israel and Sweden have got their country sites up and running. The local sites can be accessed from the Orphanet in Partner Countries section of the Orphanet homepage.


 


 
New Syndromes
 

 
New glycosylation congenital disorder due to deficiency of subunit 6 of the conserved oligomeric Golgi complex
 
Deficiency of subunit 6 of the conserved oligomeric Golgi (COG6) complex causes a new combined N- and O-glycosylation deficiency of the congenital disorders of glycosylation, designated as CDG-IIL (COG6-CDG). The index patient presented with a severe neurologic disease characterised by vitamin K deficiency, vomiting, intractable focal seizures, intracranial bleedings and fatal outcome in early infancy.
Read the PubMed abstract

 
To read more about "CDG syndrome"

 
Hum Mol Genet ; 3623-3633 ; 15 September 2010
 
Novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huët anomaly with neuroblastoma amplified sequence
 
A novel short stature syndrome in the Yakuts population is reported, characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huët anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision. This new syndrome is designated as Short stature with Optic atrophy and Pelger-Huët anomaly (SOPH) syndrome. Thirty-three of 34 patients had a 5741G/A nucleotide substitution in the NBAS gene in the homozygous state.
Read the PubMed abstract

 
J Med Genet ; 538-548 ; August 2010
 


 
New Genes
 

 
Behcet disease: two separate studies identify variants in the MHC class I, IL10, and IL23R-IL12RB2 regions
 
Two separate studies published in Nature Genetics describe the identification of variants in the MHC class I, IL10, and IL23R-IL12RB2 regions in patients with Behcet disease, a chronic systemic inflammatory disorder characterised by four major manifestations: recurrent ocular symptoms, oral and genital ulcers and skin lesions.
Read the first PubMed abstract
Read the second PubMed abstract

 
To read more about "Behcet disease"

 
Nat Genet ; 698-702 ; August 2010
Nat Genet ; 703-706 ; August 2010

 
Peroxisomal biogenesis disorder: mutations in PEX10 identified
 
The authors describe a child and an adult of normal intelligence with progressive ataxia, axonal motor neuropathy, and decreased vibration sense. Both patients had marked cerebellar atrophy. Peroxisomal studies revealed a peroxisomal biogenesis disorder. Mutations in PEX10 were found in both patients. Transfection with wild-type PEX10 corrected the fibroblast phenotype. Bile acid supplements and dietary restriction of phytanic acid were started. Peroxisomal biogenesis disorders should be considered in the differential diagnosis of autosomal recessive ataxia.
Read the PubMed abstract

 
To read more about "Peroxisome biogenesis disorder"

 
Ann Neurol ; 259-263 ; August 2010
 
Cenani-Lenz syndactyly: genomic rearrangements of the GREM1-FMN1 locus identified
 
Cenani-Lenz syndactyly (CLS) is a congenital malformation syndrome defined as complete and complex syndactyly of the hands combined with malformations of the forearm bones and similar manifestations in the lower limbs. The authors describe a 263 Kb homozygous deletion of FMN1 associated with oligosyndactyly, radioulnar synostosis, hearing loss and renal defects. A 1.7 Mb duplication encompassing both the GREM1 and FMN1 genes was also detected in a patient with isolated Cenani-Lenz-like oligosyndactyly of the hands. The phenotypes of these two patients represent new entities/syndromes within the Cenani-Lenz clinical spectrum: (1) an autosomal recessive oligosyndactyly, radio-ulnar synostosis, hearing loss and renal defect syndrome; and (2) an autosomal dominant Cenani-Lenz-like non-syndromic oligosyndactyly.
Read the PubMed abstract

 
To read more about "Syndactyly, Cenani-Lenz type"

 
J Med Genet ; 569-574 ; August 2010
 
Deletion 2q37: HDAC4 haploinsufficiency identified
 
Deletion 2q37 or monosomy 2q37 is a chromosomal anomaly involving deletion of chromosome band 2q37 and manifests as three major clinical findings: developmental delay, skeletal malformations and facial dysmorphism. To date, only large deletions of 2q37 have been reported, making delineation of a critical region and subsequent identification of candidate genes difficult. The authors present clinical and molecular analysis of six individuals with overlapping deletions involving 2q37.3 that refine the critical region, reducing the candidate genes from >20 to a single gene, histone deacetylase 4 (HDAC4). HDAC4 is a histone deacetylase that regulates genes important in bone, muscle, neurological, and cardiac development. Data presented here show that deletion or mutation of HDAC4 results in reduced expression of RAI1, which causes Smith-Magenis syndrome when haploinsufficient, providing a link to the overlapping findings in these disorders.
Read the PubMed abstract

 
To read more about "Deletion 2q37"

 
Am J Hum Genet ; 219-228 ; 13 August 2010
 
Retinitis pigmentosa: a PDE6G mutation at cause in autosomal recessive form
 
Retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration, with a worldwide prevalence of 1 in 4000. Over 30 genes and loci have been implicated in nonsyndromic autosomal-recessive RP. Here the authors confirm the contribution of PDE6G to the aetiology of RP in humans and demonstrate the positive role of the gamma subunit in maintaining phosphodiesterase activity.
Read the PubMed abstract

 
To read more about "Retinitis pigmentosa"

 
Am J Hum Genet ; 258-264 ; 13 August 2010
 
Retinitis pigmentosa: mutations in IMPG2, encoding interphotoreceptor matrix proteoglycan 2, cause an autosomal-recessive form
 
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases caused by progressive degeneration of the photoreceptor cells. The authors identified two affected families with homozygous IMPG2 gene mutations. Mutation analysis in ten additional index cases of Dutch, Israeli, Italian, and Pakistani origin with homozygous regions encompassing IMPG2 revealed five additional mutations. Most patients with IMPG2 mutations showed an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. The IMPG2 gene encodes the interphotoreceptor matrix proteoglycan IMPG2, which is a constituent of the interphotoreceptor matrix.
Read the PubMed abstract

 
To read more about "Retinitis pigmentosa"

 
Am J Hum Genet ; 199-208 ; 13 August 2010
 
Ectodermal dysplasia-syndactyly: mutations in PVRL4, encoding cell adhesion molecule nectin-4, at cause
 
Ectodermal dysplasias form a large disease family with more than 200 members. The combination of hair and tooth abnormalities, alopecia, and cutaneous syndactyly is characteristic of ectodermal dysplasia-syndactyly syndrome (EDSS). The authors identified a homozygous mutation in the PVRL4 gene in an Algerian family that not only evoked an amino acid change but also led to exon skipping in two affected families. In an Italian family with two siblings affected by EDSS, they further detected a missense and a frameshift mutation. PVRL4 encodes for nectin-4, a cell adhesion molecule mainly implicated in the formation of cadherin-based adherens junctions. Together with cleft lip and/or palate ectodermal dysplasia (Zlotogora-Ogur syndrome) due to an impaired function of nectin-1, EDSS is the second known "nectinopathy" caused by mutations in a nectin adhesion molecule.
Read the PubMed abstract

 
To read more about "Ectodermal dysplasia syndrome"

 
Am J Hum Genet ; 265-273 ; 13 August 2010
 
Kabuki syndrome: MLL2 mutations identified
 
The authors identified the gene MLL2, which encodes a Trithorax-group histone methyltransferase in a number of patients with Kabuki syndrome, a disorder characterised by a unique facial appearance, intellectual deficit, and postnatal progressive growth retardation. In families where parental DNA was available, the mutation was confirmed to be de novo (n=12) or transmitted (n=2) in concordance with phenotype. These results strongly suggest that mutations in MLL2 are a major cause of Kabuki syndrome.
Read the PubMed abstract

 
To read more about "Kabuki syndrome"

 
Nat Genet ; 790-793 ; September 2010
 
Setleis syndrome: homozygous nonsense mutations in TWIST2 at cause
 
Homozygous TWIST2 nonsense mutations were identified in patients with Setleis syndrome, a member of the focal facial dermal dysplasias, of which the characteristic diagnostic feature is bitemporal scar-like lesions that resemble forceps marks. Notably, Setleis syndrome patients and Twist2 knockout mice have similar facial features, indicating the gene's conserved role in mammalian development.
Read the PubMed abstract

 
To read more about "Facial ectodermal dysplasia"

 
Am J Hum Genet ; 289-296 ; 13 August 2010
 
Perrault syndrome: mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia
 
Perrault syndrome is a recessive disorder characterised by ovarian dysgenesis in females, sensorineural deafness in both males and females, and in some patients, neurological manifestations. No genes for Perrault syndrome have heretofore been identified. A small family of mixed European ancestry includes two sisters with well-characterised Perrault syndrome. Whole-exome sequencing of genomic DNA from one of these sisters revealed exactly one gene with two rare functional variants: HSD17B4, which encodes 17beta-hydroxysteroid dehydrogenase type 4, also known as D-bifunctional protein. Mutations in HSD17B4 are known to cause DBP deficiency, an autosomal-recessive disorder of peroxisomal fatty acid beta-oxidation that is generally fatal within the first two years of life. No females with DBP deficiency surviving past puberty have been reported, and ovarian dysgenesis has not previously been associated with this illness. Six other families with Perrault syndrome have wild-type sequences of HSD17B4. These results indicate that Perrault syndrome and DBP deficiency overlap clinically; that Perrault syndrome is genetically heterogeneous; that DBP deficiency may be underdiagnosed; and that whole-exome sequencing can reveal critical genes in small, nonconsanguineous families.
Read the PubMed abstract

 
To read more about "Perrault syndrome"

 
Am J Hum Genet ; 282-288 ; 13 August 2010
 


 
Research in Action
 

 
Fundamental Research
 
Proximal spinal muscular atrophy: PTEN depletion rescues axonal growth defect and improves motor neuron survival
 
Proximal spinal muscular atrophies are a group of neuromuscular disorders characterised by progressive muscle weakness resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei. Phosphatase and tensin homolog (PTEN), a negative regulator of the mammalian target of rapamycin (mTOR) pathway, is widely involved in the regulation of protein synthesis. Here the authors show that PTEN depletion led to an increase in growth cone size, promotion of axonal elongation and increased cell survival of these cells. These changes were associated with alterations of downstream signalling pathways for local protein synthesis as revealed by an increase in pAKT and p70S6. Most notably, this treatment also restores beta-actin protein levels in axonal growth cones of SMN-deficient motor neurons. Furthermore, the authors report that a single injection of adeno-associated virus serotype 6 (AAV6) expressing siPTEN into hind limb muscles at postnatal day 1 in SMNDelta7 mice leads to a significant PTEN depletion and robust improvement in motor neuron survival. PTEN-mediated regulation of protein synthesis in motor neurons could represent a target for therapy in spinal muscular atrophy.
Read the PubMed abstract

 
To read more about "Proximal spinal muscular atrophy"

 
Hum Mol Genet ; 3159-3168 ; 15 August 2010
 
Amyotrophic lateral sclerosis: mutant superoxide dismutase 1-induced IL-1beta accelerates pathogenesis
 
Amyotrophic lateral sclerosis is a fatal motor neuron disease of adult onset. Neuroinflammation contributes to disease progression; however, the inflammatory trigger remains unclear. The authors report that ALS-linked mutant superoxide dismutase 1 (SOD1) activates caspase-1 and IL-1beta in microglia. Their findings identify microglial IL-1beta as a causative event of neuroinflammation and suggest IL-1 as a potential therapeutic target in ALS.
Read the PubMed abstract

 
To read more about "Amyotrophic lateral sclerosis"

 
PNAS ; 13046-13050 ; 20 July 2010
 
Clinical Research
 
Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients
 
Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. In this study, the authors confirm that Stickler syndrome type 1 is predominantly caused by loss-of-function mutations in the COL2A1 On the basis of binary regression analysis, the authors developed a scoring system that may be useful when evaluating patients with Stickler syndrome.
Read the PubMed abstract

 
To read more about "Stickler syndrome"

 
Eur J Hum Genet ; 872-880 ; August 2010
 
Prader-Willi syndrome: distribution of the genetic subtypes in the elderly
 
The Prader-Willi syndrome (PWS) is a genetic disorder caused by the absent expression of the paternal copy of maternally imprinted genes in chromosome region 15q11-13. The frequencies of different subtypes in PWS are usually given in literature as 70% deletion, 25-30% maternal uniparental disomy (mUPD) and 3-5% others (imprinting centre (IC) defects and translocations). This study sample comprised 102 adults with clinically and genetically confirmed PWS. Genetic testing showed 55 persons (54%) with a paternal deletion, 44 persons (43%) with an mUPD and 3 persons (3%) with a defect of the IC. The observed distribution in this study differed from that in literature (70% deletion, 30% mUPD), which was statistically significant. This was mainly caused by a higher proportion of mUPD in the advanced age groups. In other studies, these elderly persons might have been undiagnosed and/or under-reported because of a lack of genetic diagnosis. The results underline both the need for correct genetic diagnosis in all persons with PWS and adjustment of the guidelines for preventive management in adulthood.
Read the PubMed abstract

 
To read more about "Prader-Willi syndrome"

 
Eur J Hum Genet ; 993-998 ; September 2010
 
Cohen syndrome: what are the best indicators for the presence of a VPS13B gene mutation?
 
Cohen syndrome is a rare autosomal recessive inherited disorder that results from mutations of the VPS13B gene. Clinical features consist of a combination of intellectual deficit, facial dysmorphism, postnatal microcephaly, truncal obesity, slender extremities, joint hyperextensibility, myopia, progressive chorioretinal dystrophy, and intermittent neutropenia. The authors sought to determine which clinical features were the best indicators for the presence of VPS13B gene mutations in a series of 34 patients with suspected Cohen syndrome. From this study and a review of more than 160 genotyped cases from the literature, it is concluded that, given the large size of the gene, VPS13B screening is not indicated in the absence of chorioretinal dystrophy or neutropenia in patients aged over 5 years. The follow-up of young patients could be a satisfactory alternative unless there are some reproductive issues.
Read the PubMed abstract

 
To read more about "Cohen syndrome"

 
J Med Genet ; 549-553 ; August 2010
 
Familial spastic paraplegia: 220 patients with autosomal dominant disease form do not display mutations in the SLC33A1 gene
 
The most frequent causes of autosomal dominant (AD) hereditary spastic paraplegias (HSP) (ADHSP) are mutations in the SPAST gene (SPG4 locus). However, roughly 60% of patients are negative for SPAST mutations, despite their family history being compatible with AD inheritance. A mutation in the gene for an acetyl-CoA transporter (SLC33A1) has recently been reported in one Chinese family to cause ADHSP-type SPG42. The authors screened 220 independent SPAST mutation-negative ADHSP samples for mutations in the SLC33A1 gene and did not identify potentially disease-causing mutations in the patients.
Read the PubMed abstract

 
To read more about "Familial spastic paraplegia"

 
Eur J Hum Genet ; 1065-1067 ; September 2010
 
Amyotrophic lateral sclerosis: integrative gene-tissue microarray-based approach for identification of disease biomarkers
 
The authors developed an integrative approach using animal models, postmortem human material and a combination of high-throughput microarray methods to identify novel molecular markers of amyotrophic lateral sclerosis (ALS). They used laser capture microdissection coupled with microarrays to identify early transcriptome changes occurring in spinal cord motor neurons or surrounding glial cells. Two models of familial motor neuron disease transgenic mice were used at the presymptomatic stage. This large-scale gene and protein expression study pointing to distinct molecular mechanisms of TAU- and SOD1-induced motor neuron degeneration identified several new SALS-relevant proteins (CNGA3, CRB1, OTUB2, MMP14, SLK, DDX58, RSPO2) and putative blood biomarkers, including Nefh, Prph and Mgll.
Read the PubMed abstract

 
To read more about "Amyotrophic lateral sclerosis"

 
Hum Mol Genet ; 3233-3253 ; 15 August 2010
 
Holoprosencephaly: the unfolding clinical spectrum due to mutations in the SHH, ZIC2, SIX3, TGIF, and ZIC2 genes
 
Holoprosencephaly (HPE) is a severe malformation of the brain characterised by abnormal formation and separation of the developing central nervous system. The prevalence is 1:250 during early embryogenesis, the live-born prevalence is 1:16 000. The aetiology of HPE is extremely heterogeneous and can be teratogenic or genetic.

Two recent studies explore the clinical spectrum as related to specific gene mutations. In the first study, the authors screened four known HPE genes in a Dutch cohort of 86 non-syndromic HPE index cases, including 53 family members. They detected 21 mutations, 3 in SHH, 9 in ZIC2 and 9 in SIX3. About half of the mutations were de novo, one was a germ line mosaic. The familial mutations displayed extensive heterogeneity in clinical manifestation. Of seven familial index patients only two parental carriers showed minor HPE signs, five were completely asymptomatic. Therefore, each novel mutation should be considered as a risk factor for clinically manifest HPE, with the caveat of reduced clinical penetrance.

A second study characterised the genetic and clinical findings in patients with ZIC2 mutations and found that HPE due to ZIC2 mutations is distinct from that due to mutations in other genes. This finding may shed light on the mechanisms involved in formation of the forebrain and face and will help direct genetic counselling and diagnostic strategies.
Read the first PubMed abstract
Read the second PubMed abstract

 
To read more about "Holoprosencephaly"

 
Eur J Hum Genet ; 999-1005 ; September 2010
J Med Genet ; 513-524 ; August 2010

 
Hyperplastic polyposis syndrome: increased colorectal cancer risk in first-degree relatives of patients
 
This study of 347 subjects finds that first-degree relatives of hyperplastic polyposis syndrome patients have an increased risk for both colorectal cancer and hyperplastic polyposis syndrome compared to the general population. Hence, as long as no genetic substrate has been identified, screening colonoscopies for first-degree relatives seem justified, though this needs to be prospectively evaluated.
Read the PubMed abstract

 
To read more about "Hyperplastic polyposis syndrome"

 
Gut ; 1222-1225 ; September 2010
 
Gene Therapy
 
Retinitis pigmentosa: genetic reactivation of cone photoreceptors restores visual responses
 
Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. The authors show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitised photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, they show that halorhodopsin can reactivate light-insensitive human photoreceptors.
Read the PubMed abstract

 
To read more about "Retinitis pigmentosa"

 
Science ; 413-417 ; 23 July 2010
 
Dystrophic epidermolysis bullosa: SIN retroviral vectors expressing COL7A1 under human promoters for ex vivo gene therapy
 
Recessive dystrophic epidermolysis bullosa (RDEB) is caused by loss-of-function mutations in COL7A1 encoding type VII collagen which forms key structures (anchoring fibrils) for dermal-epidermal adherence. From birth, patients suffer from skin blistering, and develop severe local and systemic complications resulting in poor prognosis. To minimize the risk of oncogenic events, the authors developed new minimal self-inactivating (SIN) retroviral vectors in which the COL7A1 complementary DNA (cDNA) is under the control of the human elongation factor 1alpha (EF1alpha) or COL7A1 promoters. They show efficient ex vivo genetic correction of primary RDEB keratinocytes and fibroblasts without antibiotic selection, and use either of these genetically corrected cells to generate human skin equivalents (SEs) which were grafted onto immunodeficient mice. They achieved long-term expression of recombinant type VII collagen with restored dermal-epidermal adherence and anchoring fibril formation, demonstrating in vivo functional correction. Despite rearranged proviruses identified in a few cases, this preclinical study paves the way for a therapy based on grafting the most severely affected skin areas of patients with fully autologous SEs genetically corrected using a SIN COL7A1 retroviral vector.
Read the PubMed abstract

 
To read more about "Dystrophic epidermolysis bullosa"

 
Mol Ther ; 1509-1518 ; August 2010
 


 
Patient Management and Therapy
 

 
Proximal spinal muscular atrophy: L-carnitine and valproic acid show no benefit
 
Valproic acid (VPA) has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA) in vitro and in vivo. The authors present the results of a multicenter phase II randomised double-blind intention-to-treat protocol in 61 non-ambulatory SMA subjects 2-8 years of age. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS) score following six months of treatment. This study demonstrated no benefit from six months treatment with VPA and L-carnitine. Weight gain, age and treatment duration were significant confounding variables that should be considered in the design of future trials.
Read the PubMed abstract

 
To read more about "Proximal spinal muscular atrophy"

 
PLoS One ; e12140 ; 19 August 2010
 
Gaucher disease type 1: oral substrate reduction therapy eliglustat tartrate shows promise
 
Eliglustat tartrate (Genz-112638), a specific inhibitor of glucosylceramide synthase, is under development as an oral substrate reduction therapy for Gaucher disease type 1 (GD1). A multinational, open-label, single-arm phase 2 study of 26 GD1 patients evaluated the efficacy, safety, and pharmacokinetics of eliglustat tartrate administered twice daily by mouth at 50- or 100-mg doses based on plasma drug concentrations. Entry criteria required splenomegaly with thrombocytopenia and/or anaemia. The composite primary efficacy end point required improvement after 52 weeks in at least 2 of these 3 disease manifestations and was met by 77% of all patients and 91% of the 22 patients completing 52 weeks. Statistically significant improvements occurred in mean hemoglobin level, platelet count, spleen volume, liver volume and lumbar spine bone mineral density. Elevated biomarkers (chitotriosidase; chemokine CCL18; angiotensin-converting enzyme; tartrate-resistant acid phosphatase) decreased by 35% to 50%. Plasma glucosylceramide and ganglioside GM3 normalised. Eliglustat tartrate was well tolerated.
Read the PubMed abstract

 
To read more about "Gaucher disease type 1"

 
Blood ; 893-899 ; 12 August 2010
 
Kennedy disease: leuprorelin does not show significant effect on swallowing
 
Spinal and bulbar muscular atrophy (Kennedy disease) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor. At present there are no treatments for spinal and bulbar muscular atrophy, although leuprorelin suppressed the accumulation of pathogenic androgen receptors in a phase 2 trial. This 48-week, randomised, double-blind, placebo-controlled trial involving 199 patients and with a primary endpoint of pharyngeal barium residue, which indicates incomplete bolus clearance, measured at week 48 by videofluorography, showed that 48 weeks of treatment with leuprorelin did not have a significant effect on swallowing function in patients with spinal and bulbar muscular atrophy, although it was well tolerated.
Read the PubMed abstract

 
To read more about "Kennedy disease"

 
Lancet Neurol ; 875-884 ; September 2010
 
Pemphigus vulgaris: mycophenolate mofetil with prednisone shows benefits in mild or moderate cases
 
Pemphigus is a group of chronic autoimmune skin diseases characterized by blister formations on the outer layer of the skin and the mucous membranes. In a prospective, multicenter trial, 96 outpatients with mild or moderate pemphigus vulgaris were randomised to mycophenolate mofetil (MMF) plus oral corticosteroids or placebo plus oral corticosteroids for 52 weeks. The primary end point was the proportion of patients in the placebo and combined MMF groups responding to treatment (absence of new, persistent oral or cutaneous lesions, and prednisone dose). MMF-treated patients showed faster and more durable responses. In post hoc analyses, more patients taking MMF showed sustained responses for 3 or 6 months than did placebo patients. MMF was well tolerated. Although MMF did not show an advantage on the primary end point, there seemed to be a beneficial treatment effect on several secondary end points, including time to response and duration of response. Thus, MMF may be a potentially useful agent in patients with mild or moderate pemphigus vulgaris.
Read the PubMed abstract

 
To read more about "Pemphigus vulgaris"

 
J Invest Dermatol ; 2041-2048 ; August 2010
 


 
Orphan Drugs
 

 
The US Orphan Drug Act and stem cell-based therapies
 
In the United States of America, the Orphan Drug Act was adopted in 1983 in order to stimulate the development of products for rare diseases. Since its adoption, scientific discovery has leapt forward and areas of promise today include innovative treatments such as gene therapy and stem cell transplantation. Though still in their early stages, these new arenas offer hope to rare disease patients, their families and care givers. An article appearing in the review Cell Stem Cell considers the burgeoning field of stem cell-based products (SCBP) in relation to the existing orphan drug legislation in the USA. The authors, members of the Office of Orphan Products Development (OOPD) of the Food and Drug Administration (FDA), evaluate the stem cell-based product applications received by their office which have been granted orphan designation. In the USA, an orphan designation requires demonstration that the indication for the product is a rare disease (a prevalence of less than 200,000 in the USA) and that there exists sufficient evidence of medical rationale to expect that the product is promising for the treatment of the given indication”. Amongst the interesting data this article supplies, “As of March 31, 2010, the OOPD received 3094 applications for orphan designation and from this granted 2156 designations (70% of all applications). … During this period, 349 orphan-designated products received marketing approval. At present, orphan-designated products comprise approximately one-third of all FDA New Molecular Entity (NME) marketing approvals". For stem cell-based products during the same time period, the OOPD has received 27 applications for orphan designation. To date, none has received marketing approval. Of the 27applications received, 78% were granted orphan designations –a slightly higher figure than the overall designation rate. Sources for stem-cell based products include human embryonic stem cells, foetal porcine cells, peripheral blood, umbilical cord blood, mesenchymal tissue, olfactory tissue, and bone marrow. The authors qualify the diversity of sources as “a reflection of the multiple avenues being utilized to reach the goal of developing SCBPs”. Amongst the rare target indications for stem cell-based products are amyotrophic lateral sclerosis, proximal spinal muscular atrophy, chronic granulomatous disease and Huntington disease.

The authors note that orphan drug application in the USA is not limited to US-based sponsors. New measures, such as the recently implemented common orphan product annual report between the FDA and the European Medicines Agency are indeed geared to encourage trans-Atlantic collaboration. To date, however, of the 27 applications only six originated from sponsors outside the USA. The authors view this as illustrating “an underutilized area of opportunity for international sponsors to capitalize on US incentives offered through the ODA for the development of SCBPs for rare diseases".

The article also reviews the translational capacities of stem cell-based products: “Many diseases that stand to benefit from SCBPs are due to heterogeneous underlying causes, yet the end clinical pathology of such disparate maladies may be comparable—as in the case of some neurodegenerative diseases. From this it stands to reason that research conducted on SCBPs under the context of a rare disease (utilizing ODA incentives) may aid in the development of SCBPs for other rare or common diseases that manifest with similar pathologies”. Amongst the common methods that have the potential to translate from one rare stem cell based-product to another rare or common disease product are “…ex vivo propagation and differentiation, techniques to control tumorigenicity or immunogenicity, analytical tools to characterize as well as confirm the identity of the final product, methodologies for (re)introduction of SCBPs that ensure directed delivery to their appropriate physiologic locations, and the development of technologies that permit noninvasive imaging to allow for monitoring of the fate of SCBPs after patient administration”.

Thus the authors evoke the “invaluable opportunity” that the Orphan Drug Act presents for sponsors to develop stem cell-based products for the treatment of rare diseases, adding that the legislation can … “hasten the development of products for often neglected populations where therapies may be nonexistent or of limited effectiveness”. In Europe, the Committee for Advanced Therapies was created within the European Medicines Agency in 2009 specifically for emerging technologies such as stem cell-based treatments. To date, over a dozen stem cell-based products have received designation in the European Union. Consult the PubMed abstract

 
Trial demonstrates that randomised controlled studies are feasible for rare diseases
 
While trial results recently published in the Lancet Neurology showed no benefit for the product being tested (ciclosporin, both alone and in combination with intermittent prednisone for the treatment of ambulant patients with Duchenne muscular dystrophy), the authors make the point that the study does demonstrate the feasibility of randomised controlled trials “with sufficient statistical power” in rare diseases. In a press release published on the website of neuromuscular disease network Treat-NMD, the trial coordinator points out that the trial has “… clearly shown that it is possible to perform meaningful randomized controlled clinical trials with sufficient statistical power even in rare diseases like DMD - which is very promising in terms of the future therapies that are now coming to trial." The press release cautions that “… as commercial interest and financial resources can still remain scarce, it is important to note that planning and carrying out such a trial requires close cooperation between researchers, clinicians, patient groups, public funding sources and industry partners. The German muscular dystrophy network MD-NET and the support of patient organizations was instrumental in this trial.”
Consult the PubMed abstract
Consult the TREAT-NMD news article

 
FDA approves Cuvposa (glycopyrrolate) to treat chronic severe drooling caused by neurologic disorders in children
 
The U.S. Food and Drug Administration has approved Cuvposa (glycopyrrolate) Oral Solution to treat chronic severe drooling caused by neurologic disorders in children ages 3 years to 16 years. A significant proportion of the developmentally disabled population experiences drooling caused primarily by neuromuscular dysfunction that makes it hard to swallow. Cuvposa reduces drooling by lowering the volume of saliva produced. Glycopyrrolate, already approved to treat peptic ulcers and reduce salivation in patients under anesthesia, has been used on an off-label basis to treat drooling in the developmentally disabled population. For further details

 


 
News from the Patients' Associations
 
International Brain Tumour Alliance celebrates its fifth anniversary with special “world edition” magazine
 
The International Brain Tumour Alliance (IBTA) is a global network of support, advocacy and information groups for brain tumour patients and carers around the world and also includes researchers, scientists, clinicians and allied health professionals who work in the area of brain tumours – all of which are rare conditions. The IBTA's two main projects - the "International Brain Tumour Awareness Week" (this year from 31 October to 6 November 2010) and the "Walk Around the World for Brain Tumours" (this year from 1 January through 6 November 2010) were supported in 2009 by 182 brain-tumour relevant organisations around the globe. The IBTA has published a 114-page magazine to mark its fifth anniversary. Interviews with patients, caregivers and many of the world's most eminent neuro-oncology specialists; articles on support groups in various countries; information on cutting-edge treatments and a range of other stories all provides a unique overview of life in the international brain tumour community. Visit the IBTA website to order a free copy.

 


 
Courses & Educational Initiatives
 

 
European Advanced Postgraduate Course in Classical and Molecular Cytogenetics
 
This ten-day course held in February/March each year is designed to provide advanced training in constitutional, haematological, and oncological cytogenetics to medical graduates, pharmacists, pathologists, biologists, health professionals and researchers, with an academic qualification. The students will be trained to identify genetic abnormalities for diagnosis and prognosis, and for fundamental and applied research using both classical and molecular cytogenetic techniques. The course is co-organised by the European Cytogeneticists Association and two French Universities, either as a stand-alone course with only the theoretical part or as a University Diploma including both theoretical and practical training. 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

 
Orphan Academy courses for 2010 and 2011
 
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

 


 
What's on Where?
 


 
XIV Meeting of the European Society for Immunodeficiencies and IX Meeting of the Int’l Nursing Group for Immunodeficiencies
 
Date: 6-9 October 2010
Venue: Istanbul, Turkey

Featuring an interesting scientific programme of clinical, laboratory and molecular findings, diagnosis, prevention and treatment for common and rare primary immunodeficiencies. Held in tandem with the XIth Meeting of the International Patient Organisation for Primary Immunodeficiencies.
For further details

 
Sixth International Network of Paediatric Surveillance Units (INoPSU) Meeting
 
Date: 7 October 2010
Venue: Dublin, Ireland

The INoPSU joins 12 diverse countries with a common purpose - to conduct surveillance of uncommon conditions of childhood. The member units span the globe - from Canada to New Zealand. This year’s keynote address will be from Orphanet.
For further details

 
2nd European Rett Syndrome Conference
 
Date: 7-10 October 2010
Venue: Edinburgh, Scotland

Sessions include clinical and molecular update on MECP2 and Rett Syndrome; non coding RNAs & brain development; lessons from other diseases and other models; treatments and trials; outcome measures, international collaborations; and current perspectives and next steps.
For further details

 
15th International Congress of World Muscle Society
 
Date: 12-16 October 2010
Venue: Kumamoto, Japan

The main topics to be addressed include new therapeutic targets for neuromuscular disorders; congenital muscular dystrophies (celebrating the 50th anniversary of Fukuyama congenital muscular dystrophy); and distal myopathies and protein aggregation myopathies.
For further details

 
26th Annual Meeting of the Histiocyte Society
 
Date: 18–20 October 2010
Venue: Boston, Massachusetts USA

This year’s scientific programme will feature presentations by several experienced researchers regarding a variety of perspectives on the histiocytic disorders.
For further details

 
Accelerating Therapies for Rare Diseases Workshop
 
Date: 18–20 October 2010
Venue: Rockport, Maryland, USA

The Food and Drug Administration (FDA), Center for Drug Evaluation and Research and the National Institutes of Health, Office of Rare Diseases Research and National Institute of Neurological Disorders and Stroke in collaboration with the National Organization for Rare Disorders and Duke University Medical Center, offer this 3-day workshop on conducting research on rare diseases and orphan products. The workshop focuses on FDAs regulatory requirements and the clinical trial issues that are especially relevant to rare disease research.
For further details

 
Future Direction for Orphan Drugs in Europe
 
Date: 3 November 2010
Venue: Le Mesnil Amelot (Paris region), France

This first conference on orphan drugs from the neutral, non-profit, global, professional Drug Information Association will reflect on the experience gained in the first 10 years of the European Orphan Medicinal Products Regulation. It will review current developments in orphan drug research, look at points of collaboration between regulatory and HTA bodies and provide an outlook on future developments.
For further details

 
Pemphigus & Pemphigoid: From the Bench to the Bedside
 
Date: 5-6 November 2010
Venue: Bethesda, Maryland, USA

The meeting will bring together physicians and scientists interested in these diseases to meet face-to-face and facilitate interactions. The goal is to identify areas of research opportunity that will promote understanding of the causes and provide experimental and clinical justification for novel treatments of pemphigus and pemphigoid.
For further details

 
Optimising Orphan Drug Development
 
Date: 15-16 November 2010
Venue: Brussels, Belgium

Key topics include: Exploring the regulatory landscape for orphan drug development; Reviewing the different reimbursement processes in the EU to achieve better market access; Overcoming developmental challenges in orphan drugs; Examining the post phase 4 and market authorisation challenges; Assessing the opportunities for orphan drug development for “big pharma”.
For further details

 
3rd European Symposium on Rare Anaemias and 1st Spanish Thalassemia meeting for Patients and Professionals
 
Date: 19-20 November 2010
Venue: Madrid, Spain

The 3rd European Symposium on Rare Anaemias is an activity of the ENERCA project, which aims to stimulate interest and inform colleagues on the subject of congenital and rare anaemias. The programme will address prevention, diagnosis, treatment and includes an interactive workshop with patient panellists and doctors, focusing not only on clinical management but also on prevention and social action for thalassaemia and haemoglobinopathies.
For further details

 
Encephalitis Professional Seminar
 
Date: 29 November 2010
Venue: London UK

This seminar presents current studies that contribute to a fuller understanding of the pathogenesis, epidemiology and outcomes of encephalitis.
For further details

 
11th EPPOSI Workshop on Rare Disease Therapy Development Workshop
 
Date: 29-30 November 2010
Venue: Prague, Czech Republic

The topics of this year’s European Platform for Patients’ Organizations, Science and Industry workshop will include: Science - the determinants of rare disease research in Europe: understanding the current and future European Research and Development challenges and opportunities; Regulation - Europe and beyond: developing future regulations and policies for better rare disease therapies; and Sustainable Access - the reality we face to improve access to and affordability of orphan drugs.
For further details

 
World Orphan Drug Congress
 
Date: 29 November – 1 December 2010
Venue: Geneva, Switzerland

Showcasing leading commercial strategies and orphan drug successes, and offering insight into the successful development, authorisation and reimbursement of rare disease drugs.
For further details

 
2nd Annual Commercialisation & Market Access Strategies for Orphan & Ultra-Orphan Drugs
 
Date: 15-16 December 2010
Venue: Barcelona, Spain

The event will be focused on orphan therapies and will guarantee all participants access to today’s most relevant case studies and views which directly affect their future business plans and can assist them to maximise market and patient access.
For further details

 
4th International Meeting on the Congenital Disorders of Glycosylation and Related Disorders
 
Date: 13-14 January 2011
Venue: Leuven, Belgium

The meeting will cover all aspects of these disorders, including the discovery of novel types, the study of fundamental aspects of glycosylation, analytical procedures and diagnostic methods and the analysis of models for the disease. The meeting is organised by EUROGLYCANET, a European network for the advancement of research, diagnosis and treatment of a growing group of rare disorders. Deadline for abstract submission: 30 September 2010.
For further details

 
VII International Conference on Rare Diseases and Orphan Drugs (ICORD 2011)
 
Date: 21-23 May 2011
Venue: Tokyo, Japan

A global meeting on international cooperation and public health policies focussing on research, diagnosis, development of and access to treatment and care for rare diseases. The programme for this conference will be available shortly.
For further details

 
Eighth European Cytogenetics Conference
 
Date: 2-5 July 2011
Venue: Porto, Portugal

This meeting will provide the participants with an opportunity for not only contributing their knowledge and experience, but also for interacting with each other. Deadline for abstract submission: 28 February 2011.
For further details

 
Treat-NMD Global Conference
 
Date: 8-11 November 2011
Venue: Geneva, Switzerland

The conference will comprise a range of sessions addressing the challenges in the neuromuscular field, including: Delivery of future therapies; Biomarkers; Care considerations; Neuromuscular diseases and society; and Regulatory issues, orphan drugs and the rare disease field.
For further details

 


 
Press & Publications
 

 
Dysphagia in Rare Conditions: An Encyclopedia
 
Authors: H. Jones, J. Rosenbek -Eds.
Publisher: Plural Publishing
ISBN: 978-1-59756-230-0

The first book to concentrate on dysphagia in rare conditions. Covering a wide range of conditions – from progressive supranuclear palsy (PSP), through connective tissue disease, to conditions as diverse as West Nile virus – the editors and expert contributors synthesise the available information to provide the essentials needed to help clinicians to perform sophisticated assessments, based on their knowledge of both the conditions and the expected swallowing signs and treatments. Each entry covers the neurology of the given condition, including the signs and symptoms, neuropathology, epidemiology and genetics. Thereafter, coverage of swallowing in each condition examines the diagnostic signs and symptoms, aetiology, swallowing neuropathology, associated cognitive, linguistic, and communicative signs and symptoms, special diagnostic considerations, treatment, nutrition, hydration, and medications.

 
Medical Informatics in a United and Healthy Europe
 
Authors: K.P. Adlassnig, B. Blobel, J. Mantas and I. Masic -Eds.
Publisher: IOS Press
ISBN: 978-1-60750-044-5

This volume contains the proceedings of the Twenty-second International Conference on Medical Informatics Europe MIE 2009, that was held in Sarajevo, Bosnia and Herzegovina, from 30 August to 2 September 2009. The scientific topics range from national and trans-national eHealth roadmaps, health information and electronic health record systems, systems interoperability and communication standards, medical terminology and ontology approaches, and social networks to Web, Web 2.0, and Semantic Web solutions for patients, health personnel, and researchers. Other topics include quality assurance and usability of medical informatics systems, specific disease management and telemedicine systems, including a section on devices and sensors, drug safety, clinical decision support and medical expert systems, clinical practice guidelines and protocols, as well as issues on privacy and security. Moreover, bioinformatics, biomedical modeling and simulation, medical imaging and visualization and, last but not least, learning and education through medical informatics systems are parts of the included topics.

 
NF-kB: A Network Hub Controlling Immunity, Inflammation, and Cancer
 
Authors: M. Karin, -Ed.
Publisher: Cold Spring Harbor Laboratory Press
ISBN: 978-0879699024

NF-kB is a critical signalling molecule in the immune system that regulates cell survival and cell death, lymphocyte responses, and inflammation. Acting as a transcription factor that can receive several inputs, it coordinates distinct gene expression programs in response to a wide variety of stimuli. Written and edited by experts in the field, this volume includes contributions covering the structure of NF-kB, its DNA-binding activity and specificity, the role of the inhibitor I-B, and canonical and alternative mechanisms of NF-kB activation. The contributors examine the physiological role of NF-kB in immune cells, as well as its functions in other tissues, such as the nervous system. Including clinical perspectives on the use of NF-kB inhibitors in cancer therapy and a historical introduction by David Baltimore, in whose lab NF-kB was discovered, this volume is a reference for cell and molecular biologists, immunologists, and pathologists interested in regulation of cell function.

 


 
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
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Louise Taylor
Contact Us
Editorial Board: Ségolène Aymé, Catherine Berens, Olaf Bodamer, Raphaël Demonchy, Helen Dolk, Anders Fasth, Laura Fregonese, 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)
For more information on the European Union Committee of Experts on Rare Diseases
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