16 May 2007 print
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Editorial
 
Orphanet is entrusted with the revision of the international classification of rare diseases
 
The World Health Organization (WHO) is launching an online project to revise the international classification of diseases (ICD), defining world standards applicable to medical and sanitary statistics. For the first time, rare diseases will be taken into account in this revision. The first meeting of the steering group in charge of coordinating the revision was held in Japan on 16-18 April this year. This revision will take place in 3 stages:

  • participation of stakeholders involving the use of an internet platform
  • publication of the draft project as a "wiki," a format similar to the online Wikipedia encyclopedia
  • elaboration of the ontology and terminology


  • Thanks to a new internet application called "ICD-10 Plus", stakeholders will be able to introduce their proposals for ICD improvements and thereby make their own contribution to the revision process. In addition, users will also be able to consult other users’ proposals and discuss subjects on a blog. The proposals will be examined by groups of experts and will facilitate the elaboration of the ICD-11 project.

    The WHO has created various consultative topic groups expected to play a role in the planning and coordinating activities involved in the revision process. They incorporate the international teams in charge of the revision work and are presided by:

  • S. Ayme (France) for rare diseases
  • S. Hyman (USA) for mental health
  • J. Harrison (Australia) for external causes
  • K. Sugano (Japan) for internal medicine


  • Other groups are currently being set up. A steering group for the revision will control the coordination and Prof. Christopher Chute from the Mayo Clinic College of Medicine in the USA will preside over all tasks of general interest.

    Former ICD revisions are founded on annual conferences attended by a limited number of selected experts. Thanks to this new platform, the WHO will collaborate with interested parties, governmental organisations and NGOs, universities, industry and the general public, to ensure that the new classification system corresponds as closely as possible to their needs. Three distinct versions of the new ICD are envisaged: a concise version for primary healthcare, a detailed version for use in a specialised framework and a specialised version for research purposes.

    The "Coding and Classification" Working Group of the Rare Disease Task Force held a meeting in Paris on 2 May in order to discuss the way to start the ICD10 revision process. The members of this WG are the core representation of the WHO Topic Advisory Group for rare diseases, which needs to be completed with experts from other regions of the world. The NIH was represented by Stephen Groft, who expressed the NIH's willingness to participate in the revision process. The minutes of this meeting will be available shortly.

    Consult the WHO press release


     


     
    Task Force Update
     

    The next Rare Disease Task Force meeting will be held in Luxembourg on 20 June 2007. The precise venue will be confirmed at a later date. Members are kindly requested to confirm their participation or nominate a representative by 15 May.

    The RDTF / WHO Coding & Classification meeting was held in Paris on 2 May. The minutes will follow shortly.

    Don’t forget, for more information about the Rare Diseases Task Force readers may consult the DG SANCO rare diseases website


     


     
    EU Policy News
     
    EU Parliament gives green light to stem cell and other Advanced Therapies Regulation
     

    Many among the rare disease community across Europe breathed a collective sigh of relief last month as the European Parliament adopted Advanced Therapies Regulation despite calls for ethical amendments focusing on the inclusion of potential treatments involving human embryonic stem cells and human-animal hybrid embryos. The new rules passed on 25 April this year consolidate the 27-member-state mosaic of regulatory schemes into a global EU marketing approval and monitoring procedure for the so-called "Advanced" therapies, which include gene therapy, adult stem cell therapy and tissue engineering. These therapies are considered to have great potential for curing degenerative diseases such as Parkinson's and Alzeimer's, and many other much rarer disorders, and are also widely considered to have a potentially positive economical impact on the Community. The Regulation was adopted by 403 MEP votes to 246, with 11 abstentions.

    Strong opposition to the rules came largely from a political alliance formed by Italy, Germany and Eastern European countries including Poland, which called for additional ethical safeguards. The leader of these political detractors of the Regulation was the Slovakian Parliament rapporteur Miroslav Mikolasik, who attacked the rules which he qualified as "utilitarian" and "commercial" in their approach by arguing that the EU stamp should not be granted to products banned by certain EU countries on moral grounds.

    However, the draft Regulation adopts an interesting attitude to the problem of national ethical sensitivities in that it aims to ensure the safety and efficiency of therapies rather than their ethical acceptability, which will be addressed by individual Member States through national legislation. The rules thereby allow authorisation of all products, but simultaneously manage to preserve Member States’ rights to reject the projects in their own countries on ethical grounds. This means in practice that authorised EU therapies are subject to national approval, respecting countries such as Italy and Poland, where human ES research is banned. Gunter Verheugen, the Commission Vice-President, summed up the satisfaction of Regulation supporters, saying that the new rules unleashed the EU potential for innovation, which was often driven by SME's (small-medium-size enterprises), while also managing to respect decisions by Member States on ethical issues.

    Patient groups and the Euro biotech sector have welcomed the Regulation, which is now expected to undergo fast-track implementation by as early as mid-2008, with a mandatory review of the Regulation’s scope and functioning scheduled in five years' time.

    For more details about this important legislation, read the European Parliament press release (25 April 2007)


     
    A European registry for human embryonic stem cell lines is to be launched by the Commission
     

    The European Commission recently announced plans for the creation of a European registry for human embryonic stem cell lines. Its chief objective will be to provide comprehensive data on stem cell lines available in Europe. Funded to the tune of €1 million by the 6th Framework Programme (FP6), this project will take place over a 3-year period and will aim to provide a publicly accessible website with high-quality cell line data.

    The European registry will cover developments of particular interest, such as clinical trials, as well as information on ongoing and future EU projects in this field currently using 81 lines. The Commission's policy is to integrate the registry, the largest initiative of its kind in the world, into its research programme to maximise the use of existing stem cell lines for the improvement of the coordination and efficiency of human embryonic stem cell (hESC) research in Europe. Its independent Ethics Advisory Board will provide tight ethical limits and appropriate guidance regarding issues such as data protection, respecting what European Science and Research Commissioner, Janez Potocnik, has called a "strict and transparent working environment". This is especially important given Europe’s exemplary role in this field on the international stage. Ten European countries are involved in the registry: Belgium, the Czech Republic, Denmark, Finland, France, Germany, Spain, Sweden, the Netherlands and the UK – all countries that are already active in hESC research. Its two chief operators will be the Centre of Regenerative Medicine in Barcelona and the Berlin-Brandenburg Centre for Regenerative Therapies in Berlin.

    More about EU-funded projects and stem cells

    Find out about the Regenerative Medicine "Who's Who"


     
    Call for readers' comments on the Working Document on personal health data processing for electronic health records
     

    Members of the Article 29 Working Party of the recently-adopted Working Document on the processing of personal data relating to health in electronic health records (EHR) invite comments from medical and healthcare professionals, medical service providers (persons and institutions) and the general public.

    Read the Working Document on the processing of personal data relating to health in electronic health records (EHR), adopted on 15 February 2007.


    Deadline for comments: 13 June 2007

    Please address your comments to:

    Secretariat of the Article 29 Working Party
    European Commission, Directorate-General Justice, Freedom and Security
    Unit C.5 – Protection of personal data
    Office: LX 46 1/43
    B - 1049 Brussels
    E-mail: Click here
    Fax: +32-2-299 80 94

     


     
    National & International Policy Developments
     
    Results of Italy's call for proposals on rare diseases
     

    The Italy-USA Agreement Commission on Rare Diseases has announced it is to fund 80 research projects for a total amount of €5 million. Thirty-five Italian institutions took part in 184 projects, all of which were evaluated by foreign reviewers. This funding is a result of the Italy-USA agreement on rare diseases, for which Italy’s Istituto Superiore di Sanità launched its 2nd national call for proposals on rare diseases in 2006. The selected projects will be funded by the Italian Ministry of Health and will take place over a 2-year period.


     
    Other European news
     
    Online access to presentations made at the ESH-EBMT Euroconference on Biobanking, 9 March 2007
     

    Readers may be interested to know that the Powerpoint presentations made at this ESH-EBMT event (European Society of Haematology-European Blood and Marrow Transplantation) are now available via the ESH website.

    Click here for access to the Conference slides

     
    Other International News
     
    Results of CORD’s 1st Canadian Conference on Rare Disorders and Orphan Products Policy
     

    Canada's first Conference on orphan products policy for rare diseases, organised by the Canadian Organization for Rare Disorders (CORD), was held in Ottawa last month. The chief aim of this event, apart from establishing a clearly identified Canadian approach to the problem, is to develop a specifically Canadian policy able to produce new orphan medication, promote a new values-based access process that is both transparent and sustainable to serve patients with rare diseases in Canada.

    Durhane Wong-Rieger, CORD's President, encouraged by the support and interest in the event, including a high standard of expertise and experience demonstrated by the international group hailing from Canada, the US, Brazil and Europe, concluded that CORD was making real progress in its efforts to move the RD policy process forward.
    To access the slides of the presentations made at this conference, click here


     


     
    Ethical, Legal & Social Issues
     
    ESHRE Task Force on Ethics and Law 12: an article on oocyte donation for non-reproductive purposes
     
    Authors: ESHRE Task Force on Ethics and Law including G. Pennings1, G. de Wert, F. Shenfield, J. Cohen, B. Tarlatzis and P. Devroey
    Publisher: Oxford Journals
    1 May 2007

    This article from the Belgian ethical and legal group, the Human Society of Human Reproduction & Embryology focuses on oocyte donation for non-reproductive purposes, i.e. research and future therapy. The general principles of research ethics apply to these interventions. The proportionality principle demands that any possible harm to oocyte donors should be proportionate to all possible resulting benefits for society. The non-maleficence principle states that every reasonable effort should be made to minimize risks for donors. The position is adopted that, mutatis mutandis, women who donate oocytes for research should be treated similarly to research participants in clinical trials. This implies, among other things, that oocyte donors for research should receive reimbursement for all costs of the procedure and should get compensation for the time lost and inconvenience suffered during the treatment. In order to avoid malpractice and exploitation of poor women, a number of measures are proposed such as a ban on the import of oocytes.

    More about this article

     
    A UN Global Forum demonstrates how technological advances are helping to bring disability into the mainstream
     

    The first Global Forum of the UN Global Initiative for Inclusive Information and Communication Technologies (ICT), held a few weeks ago at the UN headquarters in New York, presented a wide array of assistive technologies which it claims are helping disabled people integrate into the workforce and thereby into society at large. Arguing that modern technology should clearly be helping employers to bring work to people with special needs, rather than attempting to bring this potential workforce to the workplace where the disability makes this impossible, accessibility experts and corporation executives mapped out a field of products designed to present some real solutions.

    Multi-nationals such as IBM, Yahoo, Internet Speech, etc showcased their latest accessible products at the forum, attended by some 200 representatives of industry, government, academia and civil institutions. In addition, government regulations are helping bring about positive developments, including centres such as the National Center for Accessible Media. Statistics in this field indicate that, for example, in Canada 90 per cent of TV programmes must be captioned, whilst in the UK up to 5 per cent of TV programmes must feature a sign language translator. Other countries including Japan, Mexico and Australia are working on similar legislation to make TV more accessible. The World Wide Web Consortium, the leading technology standard organization for web technology, recognizes the Web’s ability to make concessions to accessibility, as well as the importance of technology developments and keeping policy frameworks up-to-date with the technology. This forum was organised in cooperation with the Secretariat of the Convention on the Rights of Persons with Disabilities.


     


     
    EU Project Follow-up
     
    The NeuroNE NoE: Pharmaxon develops 3 RD programmes for the NoE
     

    Pharmaxon is a French biopharmaceutical company specialising in the development of innovatory therapies for lesions, diseases and tumours in the nervous system. It forms part of the European Network of Excellence, NeuroNE, financed by the EU as part of the Sixth Framework Programme (FP6). The network consists of 22 teams of academic researchers and 5 biotech companies, including Pharmaxon and specialises in the research of new therapies for degenerative disorders and lesions in the nervous system. Some of the network's developments also originate from a collaborative research project financed by the EU for which Pharmaxon has acquired patent rights. The company has also created collaborative actions with public research centres or European companies.

    Pharmaxon’s researchers have recently discovered new factors capable of modifying cellular migration and axonal growth and have thereby established a new therapeutical approach: the use of adhesion molecules to modulate cellular migration and neuronal growth.

    Created in 2004, the company is situated at the Institute of Biology and Development in Marseille, France. Its main field of activity is the development of treatments for the following 3 disorders:

    - severe medullar traumatic lesions, a rare disease, with 30,000 new cases per year worldwide,
    - glioblastoma, a rare cerebral tumour, also with 30,000 new cases per year,
    - Alzheimer’s disease.


    Read more about the NeuroNE project

     


     
    Orphanet News
     
    The Orphanet Germany Yearbook is launched in Bonn
     

    The Orphanet Germany Yearbook ("Handbuch Seltene Krankheiten – Orphanet Deutschland 2007") was publicly launched on 21 April by the First Lady of the Federal Republic of Germany, Eva Koehler, at a special press conference held during the annual meeting of the German Alliance for Chronic Rare Diseases (ACHSE) of which she is patron. This Yearbook represents the first initiative in Germany to collect and make a critical assessment of information on rare diseases and RD management. Funded by the European Commission and the Medical School of Hannover, the book is expected to prove a useful tool for healthcare professionals involved in RD patient management across Germany, and notably for helping patients and their families locate relevant specialists and networks for their own particular disorder.

    In both her address to the press and in her foreword written specially for the Yearbook, Eva Koehler highlighted the fact that rare diseases represent an enormous challenge to the German healthcare system. She pointed out that this was largely because Germany, unlike many other countries in Western and Northern Europe, does not have a national centre for rare diseases, a fact which greatly reduces the visibility of RD activities in Germany.

    Joerg Schmidtke, who is Coordinator of Orphanet Germany, one of Orphanet’s 35 national partners, and Professor of Human Genetics at the Medical School of Hannover Hospital, is convinced the Yearbook will prove to be a mine of practical information both for researchers and patients. However, as he points out in his introduction to the book, of which more than 40,000 copies are being distributed free of charge to physicians across Germany, the information provided in the hard copy version represents only a small part of the data available in the on-line version, the use of which he strongly recommends.



    (from left to right) Eva Koehler, First Lady of the Federal Republic of Germany and Partron of the Alliance of Chronic Rare Disorders; Joerg Schmidtke, Orphanet coordinator Germany, and Christoph Nachtigaeller, Secretary of the Bundesarbeitsgemeinschaft Selbsthilfe.

    Read more about the Orphanet Germany Yearbook on the Homepage of the President of the Federal Republic of Germany (in German only)

     
    New Texts
     
    New Orphanet Journal of Rare Diseases publications
     
    Central core disease
    Hypoplastic left heart syndrome
    Oesophageal atresia
    Craniopharyngioma
    Pyoderma gangrenosum
    Intestinal epithelial dysplasia (Tufting enteropathy)
    Malignant hyperthermia
    Paraneoplastic neurological syndromes

    and in the European Journal of Human Genetics (in association with Orphanet):
    Joubert syndrome (and related disorders)

     
    New Research Projects open for Recruitment
     
    National Multicentre trial in France for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

    Multicentre Phase III international trial in Estonia for Locally Advanced and/or Metastatic Renal Cell Carcinoma

    International multicentre clinical trial in France for Veno-Occlusive Disease (VOD) in Pediatric Stem Cell Transplantation
    Above multicentre trial in Germany
    Above multicentre trial in the Netherlands

    An Open-Label, multicentre, Phase I trial in France for Metastatic Hormone Refractory Prostate Cancer Patients
    Above multicentre trial in Belgium

     


     
    New Syndromes
     
    Osteopoikilosis, short stature and intellectual deficiency : a new syndrome associated with a 12q14 microdeletion
     

    Three unrelated patients manifest a mild intellectual deficiency, failure to thrive in infancy, proportionate short stature and Osteopoikilosis. In each patient, a heterozygous deletion in the 12q14 region appeared as a de novo event. The 3.44 Mb common area deleted contains 13 genes, including LEMD3 already involved in patients affected by Osteopoikilosis.

    Read the Pubmed article

     
    Journal of Medical Genetics ; 44(4):264-8 ; Apr 2007
     
    Deafness and masculine sterility are caused by a 15q15.3 deletion
     

    Three families manifest deafness-infertility syndrome (DIS) transmitted in an autosomal recessive mode. A common deletion approximately 100 kb long in the 15q15.3 region has been identified in individuals affected and in families carrying the disorder.

    Read the Pubmed article


     
    Journal of Medical Genetics ; 44(4):233-40. ; Apr 2007
     
    A novel intellectual deficiency syndrome is associated with a microdeletion on the 15q24 region
     

    Four patients carrying a de novo deletion on the 15q24 region manifest common characteristics: intellectual deficiency, microcephaly, digital abnormalities, hypospadias, loose connective tissue and facial dysmorphia.

    Read the Pubmed article

     
    Human Molecular Genetics ; 16(5):567-72 ; Mar 2007
     
    Severe intellectual deficiency associated with epilepsia in 2 sisters
     

    Two sisters born by consanguineous parents show a severe intellectual deficiency associated with epilepsia, hypoplasia of the terminal phalanges and an anteriorly displaced anus. A whole genome linkage scan has identified 2 homozygous regions: one of 28-Mb on the 1p chromosome, the other of 65 Mb on chromosome 14. Although characterized by clinical signs which are close to those of the Coffin-Siris syndrome, this autosomal recessive phenotype probably constitutes a new entity.

    Read the Pubmed article

     
    Clinical Dysmorphology ; 16(2):73-6 ; Apr 2007
     


     
    New Genes
     
    Loss of expression in T-box transcription factor EOMES leads to pronounced microcephalia by delayed motor growth & hypotonia
     

    Four patients born of a consanguineous family manifest a microcephaly associated with bilateral polymicrogyria and corpus callosum agenesis. A homozygous translocation between chromosomes 3p and 10q account for the recessive transmission. A position effect at the breakpoint on chromosome 3 extinguishes the expression of the EOMES gene, coding a transcription factor that is probably implicated in the division and/or the neuronal migration.


    Read the Pubmed article

     
    Nature Genetics ; 39(4):454-6 ; Apr 2007
     
    Variants in NALP1 gene are associated with different vitiligo-associated auto-immune diseases
     

    The autoimmune and autoinflammatory diseases may be due to the combination of genetic and environmental risk factors. American researchers have studied the connection between nucleotide variations on the 17p13 region and autoimmune and autoinflammatory diseases presenting a common epidemiology. Variants of the NALP1 gene, encoding a regulator of the innate immune system are associated with different combinations of autoimmune diseases including vitiligo. The innate immune system therefore appears to be implicated in the pathogenesis of these diseases.


     
    NEJM ; 356(12):1216-25. ; Mar 2007
     
    The absence of CHFR1 and CHFR3 genes increases the risk of developing atypical hemolytic and uremic syndrome
     

    Atypical hemolytic and uremic syndrome is characterised by microangiopathic haemolytic anemia, thrombocytopenia and acute renal failure. It is usually associated with mutations affecting the control of the alternate pathway of the complement. A study of two independent cohorts by German and British researchers showed that heterozygote or homozygote deletions of the CHRF1 and CHFR3 genes, 2 genes close to factor H gene that regulates the alternate pathway of the complement, are linked to an increased risk of developing an atypical form of the syndrome. The absence of expression of these 2 genes in the patients' serum leads to a partial loss of erythrocytes protection against the activation of the complement, suggesting that these 2 factors play a role in this process.

    To read more about "Hemolytic uremic syndrome, atypical form"

     
    PLoS Genet. ; 3(3):e41 ; Mar 2007
     
    A recurrent mutation in the MED12 gene identified in families affected by Opitz-Kaveggia syndrome
     

    Opitz-Kaveggia syndrome is and X-linked disorder characterised by an intellectual deficiency, macrocephaly, hypotonia and constipation. Using a gene candidate approach, American researchers have identified the same missense mutation affecting the MED12 gene in 6 families. MED12, localised in Xq13, encodes a sub-unit of the Mediator complex, required for the activation and transcriptional suppression dependent on the thyroid hormone. The in silico analysis of this substitution suggests a loss in secondary protein structure.

    To read more about "Opitz-Kaveggia syndrome"

     
    Nature Genetics ; 39(4):451-3 ; Apr 2007
     
    Leucoencephalopathy associated with a lactate elevation is due to aspartyl-tRNA synthetase deficiency
     

    Leucoencephalopathy implicating the brain stem and spinal cord, and associated with lactate elevation, is an autosomal recessive disorder which appears in early childhood. It is marked by progressive cerebellous ataxia and occasionally by slight intellectual deficiency. Using a linkage analysis, Scheper et al. have identified mutations in the DARS2 gene, encoding mitochondrial asparyltRNA syntase. Despite a reduction in enzymatic activity of the mutant proteins, researchers have not observed any variation in the mitochondrial complex activity of fibroblasts and lymphoblasts derived from patients.


     
    Nature Genetics ; 39(4):534-9 ; Apr 2007
     
    TREX1 mutations causing dominant forms of chilblain lupus and Aicardi-Goutieres syndrome
     

    Patients affected by chilblain lupus manifest skin ulcers in extremities, a clinical sign also observed in children affected by Aicardi-Goutières syndrome. In addition, the AGS1 locus containing the TREX1 gene involved in the Aicardi-Goutières syndrome, has recently been associated with chilblain lupus. For the first time, British researchers have identified heterozygous TREX1 mutations provoking chilblain lupus in a Bangladeshi family and a dominant form of Aicardi-Goutières syndrome in a Scottish child. These results suggest that certain TREX1 mutations cause a dominant transmission of this syndrome or of chilblain lupus.


     
    To read more about "Aicardi syndrome"

     
    The American Journal of Human Genetics ; 80(4):811-5 ; Apr 2007
     
    Shwachman-Bodian-Diamond syndrome (SBDS) gene mutations cause Sedaghatian-type spondylometaphysial dysplasia (SMD)
     

    Two patients with clinical signs characteristics of Sedaghatian-type spondylometaphysial dysplasia, (ie. platyspondylia, flatness of the vertebral bodies), a lacy iliac crest and acute metaphysal dysplasia, are carriers of SBDS gene mutations already implicated in Shwachman-Diamond syndrome.

    Read the Pubmed article
    "To read more about Spondylometaphyseal dysplasia"

     
    J Med Genet. ; 44(4):e73 ; Apr 2007
     


     
    Research in Action
     
    Fundamental Research
     
    The JARID1C gene, implicated in X-linked intellectual deficiency, encodes a new demethylase of the H3 histone
     

    JARID1C gene mutations are associated with a moderate to severe intellectual deficiency American researchers have recently shed light on the function of this gene situated on the X-chromosome. The JARID1C protein is a carrier of an enzymatic activity capable of transforming lysine 4 trimethylated from H3 histone to di- or mono-methylated lysine. This demethylase activity, also carried by other members of the JARID1C family, suggests for the first time that the trimethylation of histones is a reversible modification modulating the transcriptional regulation. The mutations identified in patients reduce the enzymatic activity of JARID1C, whilst studies carried out on zebrafish or on mammalian cells primary culture demonstrate a role of the enzyme in neuronal survival and the development of dendrites.

    To read more about "Mental retardation, X-linked, syndromic, due to JARID1C mutation"

     
    Cell ; 128(6):1077-88 ; Mar 2007
     
    Huntington’s disease-like 2 is associated with CUG repeat-containing RNA foci
     

    Huntington's disease-like 2 is a progressive neuronal degeneration due to the expansion of CAG/CTG triplets in an alternatively transcribed exon of the JPH3 gene. According to the splicing, these repeats can encode polyalanine or polyleucine sequences which do not seem implicated in the disease's pathogenesis, or can be transcribed within the 3' untranslated region. Rudnicki et al. have shown that the expression of a transcript carrying untranslatable CUG repeats, leads to the forming of toxic RNA foci, and could contribute to the disease's pathogenesis.

    To read more about "Huntington disease"

     
    Ann Neurol. ; 61(3):272-82 ; Mar 2007
     
    Antioxidants increase the lifetime of neurofibromatosis type 1 model fruit flies
     

    Neurofibromatosis-1 results from mutations in the NF1 gene which encodes the neurofibromin, a tumour-suppressor protein. Drosphila which carry gene mutations have a reduced life expectancy, increased sensitivity to oxidative stress and heat associated with a diminished mitochrondrial respiration and increased production of oxygen-reactive species. This phenotype is modulated by cyclic AMP/protein kinase A pathway. By administering a catalytic antioxidant to these mutant flies, the researchers managed to re-establish a normal life expectancy. This study suggests that the use of an antioxidant could be a new therapeutic pathway to explore in patients affected by neurofibromatosis-1. It also illustrates the interest of studying mechanisms linked to a pathology in a simple animal model such as a fly.

    To read more about "neurofibromatosis type 1"

     
    Nature Genetics ; 39(4):476-485 ; Apr 2007
     
    Absence of diacylglycerol kinase delta could be associated with epilepsia in humans
     

    Lennox-Gastaut syndrome is an acute epileptic encephalopathia of children. In this study, researchers have identified a translocation between Xp11.2 and 2q37 in a young girl affected by the syndrome. The 2q37 breaking point cuts the DGKD gene, encoding the diacylglycerol kinase delta. The study of this gene in mice and drosophila suggests its implication in the development of the central nervous system and a possible role in the etiology of epileptic syndromes.

    To read more about "Lennox-Gastaut syndrome"

     
    The American Journal of Human Genetics ; 80(4):792-9 ; Apr 2007
     
    Clinical Research
     
    A new risk factor in schizophrenia identified due to an association already known with the DISC1 gene
     

    In Finland, familial forms of schizophrenia have been associated with certain haplotypes of the DISC1 gene. Through studying the same Finnish families, researchers have re-analyzed their genome-wide scan data. This novel study has made it possible to highlight the link between a gene haplotype encoding NDE1, a protein interacting in a functional way with DISC1, and schizophrenia. These results illustrate the possibility, taking into account initial discoveries, of identifying new genetic factors participating with the complex etiology of multifactorial diseases.

    To read more about "Schizophrenia, Genetic Types"

     
    Human Molecular Genetics ; 16(5):453-62 ; Mar 2007
     
    An intronic mutation in RB1 responsible for a familial form of retinoblastoma
     

    The retinoblastoma is a rare ocular tumour which develops in the retina of children, due to RB1 gene mutations. In 2 affected brothers, researchers were unable to identify mutations in the genomic coding sequence of the RB1 gene. However, the analysis of the complementary DNA entire sequence has revealed an insertion of 103 pb leading to a premature arrest of the translation. This insertion, caused by an intronic mutation creating a cryptic splicing site, demonstrates the advantage of analysing the complementary DNA sequence rather than that of the exons obtained from genomic DNA.

    To read more about "Retinoblastoma"

     
    European Journal of Human Genetics ; 15(4):473-7 ; Apr 2007
     
    Two thirds of nephrotic infantile syndromes are explained by mutations in just 4 genes
     

    Mutations in the NPHS1, NPHS2, WT1 and LAMB2 genes are implicated in different infantile nephrotic syndromes. Researchers have analysed these 4 genes in a European cohort of 89 children from 80 families. They identified causal mutations in 66.3 per cent of cases (22.5 per cent in NPHS1, 37.5 per cent in NPHS2, 3.8 per cent in WT1 and 2.5 per cent in LAMB2). Some of the phenotypes observed were probably due to alterations in other genes. In addition, the NPHS1 mutations were only identified in congenital forms of these syndromes. The study also reveals the inefficacity of steroid treatments in patients who are carriers of mutations in any of these 4 genes.

    To read more about "Mesangial sclerosis, diffuse"
    To read more about "Microcoria - congenital nephrosis"
    To read more about "Congenital nephrotic syndrome, finnish type"
    To read more about "Nephrotic syndrome, idiopathic, steroid-resistant, familial"

     
    Pediatrics ; 119(4):e907-19. ; Apr 2007
     
    G6PD deficiency protects hemizygous males against malaria but not heterozygous females
     

    Mutations in the gene encoding glucose-6-phosphate deshydrogenase (G6PD) situated on the X-chromosome is the cause of an enzyme deficit which, in hemizygous males, offers protection against malaria. African and American researchers have looked for possible protection against this infection in heterozygous females in a Mali and a West African rural population. Their study confirms the positive natural selection exercised on this deficiency by the absence of infection by plasmodium falciparum in hemizygous males. However, heterozygous females do not benefit from the protective effects of this mutation.

    To read more about "Glucose-6-phosphate-dehydrogenase deficiency"

     
    PLoS Med. ; 4(3):e66 ; Mar 2007
     
    672 databases on human mutations grouped together on the same website
     

    The Human Genome Variation Society collects, organises and updates a database bringing together other bases and collecting different information on mutations and human genomic variations. The Society’s website, which has recently been updated, today includes 672 databases. This is a total of 2,056 genes and represents 32% of genes for which at least one mutation has been identified.


     
    Nature Genetics ; 39(4):425 ; Apr 2007
     
    Therapeutic Approaches
     
    Stat5 constitutive activation restores the SMN deficit observed in spinal muscular atrophy
     

    Spinal muscular atrophy is a neuromuscular disease characterised by motor neuron degeneration in the anterior horn of the spinal cord, due to SMN1 gene mutations. A therapeutic approach involves increasing the expression of the SMN2 gene expression, a SMN1 homologue encoding a functional but unstable SMN protein. By treating the human and murine cells with sodium vanadate, trichostatin A or aclarubicin, researchers observed an increase in the SMN2 expression induced by Stat5 activation. Complementary experiments suggest that Stat5 signalling regulates the transcriptional activity of the SMN2 promoter, making this signalling pathway a new potential pharmacological target for the treatment of spinal muscular atrophy.

    To read more about "Proximal spinal muscular atrophy (generic term)"

     
    Human Molecular Genetics ; 16(5):499-514 ; Mar 2007
     
    The mutant Huntingtin protein sequesters a urea cycle regulator
     

    Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide expansion in the Huntingtin gene. Using 2 mouse models of HD, Chiang et al. demonstrate that urea cycle deficiency is a prominent feature of HD. In addition, they showed that the mutant Huntingtin protein sequesters C/EBPalpha, a factor regulating the transcription of enzymes in the urea cycle. By giving the mouse models a low-protein diet, they observed an increase in the C/EBPalpha activity, re-establishing a urea cycle as well as an increase in the motor function of mice. Treatments aiming to re-establish the urea cycle thereby represent a new therapeutic approach to Huntington’s disease.

    To read more about "Huntington disease"

     
    Human Molecular Genetics ; 16(5):483-98 ; Mar 2007
     


     
    Patient Management and Therapy
     
    Cluster headache treated by electrode implantation in the sub-occipital region
     

    Cluster headache is a condition found essentially in male, young adults. The pain experienced features continuous, excruciatingly severe, orbito-facial attacks occurring several times a day briefly over periods of several weeks separated by intervals of complete remission. Eight British patients with medically intractable chronic cluster headache were implanted in the suboccipital region with electrodes stimulating the occipital nerves. Six of them noted sufficient improvements for them to recommend this treatment to other patients. The device’s major inconvenience is the swift return of headache attacks whenever the equipment malfunctioned (eg. in the case of battery depletion).

    To read more about "Cluster Headache"

     
    The Lancet ; 369(9567):1099-106 ; Mar 2007
     
    Optic Pathway Gliomas in neurofibromatosis-1 : controversies and recommendations
     

    Optic Pathway Gliomas are observed in 15-20 % of patients affected by neurofibromatosis-1. The Annals of Neurology journal proposes a panorama on pathophysiological data accumulated over the past 10 years in these tumours. The authors examine the current controversies on both the diagnosis and management involving these gliomas and propose a series of recommendations for clinicians caring for children affected by neurofibromatosis-1.

    To read more about "Neurofibromatosis type 1"

     
    Ann Neurol. ; 61(3):189-98 ; Mar 2007
     


     
    Orphan Drugs
     
    Six EMEA orphan designations for April 2007
     

    The COMP (Committee for Orphan Medicinal Products) adopted the following 6 positive opinions on orphan medicinal product designation at its April meeting for the treatment of:

    - osteosarcoma
    - pancreatic cancer
    - gastric carcinoid
    - haemophilia B (congenital factor IX deficiency)
    - 2 substances for the treatment of renal cell carcinoma

    Consult the European Registry for Orphan designations
    Check out the Orphanet list of 35 marketed orphan drugs in Europe

     
    EMEA reports its first accelerated assessment for an orphan drug
     

    The Committee for Medicinal Products for Human Use (CHMP) last month adopted a positive opinion for the orphan medicinal product, Soliris (eculizumab), after a 147-day review, making it the first medicinal product for human use to be evaluated by accelerated assessment. The EMEA review time clearly fell within the limit of 150 days set by EU legislation for accelerated assessment. The treatment is intended to reduce haemolysis (destruction of red blood cells) in patients with paroxysmal nocturnal haemoglobinuria (PNH), a rare blood disorder.

    Accelerated assessment practice was introduced by revised EU pharmaceutical legislation in November 2005. This new regulatory tool aims to help speed up patient access to new medicines of major public health interest. Companies may request accelerated assessment, provided they are able to demonstrate that their drug responds to medical needs hitherto unmet or provided it significantly improves the available methods of prevention, diagnosis or treatment of a given condition. In 2006, the CHMP received 13 requests for accelerated assessment, 4 of which were accepted.

    The Solaris opinion will next be sent to the European Commission for adoption of a marketing authorisation decision. It is worth noting that Soliris is also the first product submitted by a company benefiting from specific incentives for small and medium-sized enterprises (SMEs) to receive a positive opinion.

    Read the Guideline on the Procedure for Accelerated Assessment - Article 14 (9) of Regulation (EC) No 726/2004

     
    A new treatment for genetic disorders caused by nonsense mutations
     

    A new treatment targeting genetic disorders caused by nonsense mutations was announced in "Nature" journal last month with a preclinical development study by PTC Therapeutics. PTC 124, which is currently in phase II clinical trials for Duchenne muscular dystrophy (DMD) and Cystic fibrosis (CF), has been granted fast-track designation and orphan drug designation by the FDA for the treatment of both cystic fibrosis and Duchenne muscular dystrophy caused by nonsense mutations. The EMEA has also given PTC124 orphan drug designation for the treatment of both CF and DMD.

    Read the article in Nature Journal (Advance Online Publication) 22 April 2007 Nature05756

    More about the PTC 124 treatment

     
    Gleevec® shows favourable results for primary gastrointestinal stromal tumour at a NIH trial
     

    Preliminary results from a large, randomized, placebo-controlled clinical trial in the US for patients with primary gastrointestinal stromal tumour (GIST) demonstrated that patients treated with Gleevec® (imatinib mesylate) after removal of their tumour were significantly less likely to experience recurring cancer compared to those who were not treated with the drug. The trial was sponsored by the National Cancer Institute (NCI), part of the US National Institutes of Health (NIH).


     
    To read more about "Gastrointestinal stromal tumor"

     
    A new pharma alliance to develop plasma-based orphan drugs
     

    Kedrion and ProMetic BioTherapeutics have formed an alliance aiming to develop orphan drugs derived from human plasma, using a manufacturing procedure for which ProMetic holds the rights. The two companies are planning to select proteins which may be transformed into medical products that have already received orphan drug designation or could potentially receive it.


     


     
    Grants
     
    ELA Research Foundation call for research proposals 2007
     

    The ELA Research Foundation invites the international scientific community to submit research applications in the field of genetic leukodystrophies, cerebral white matter injury of the premature infant and myelin repair.

    ELA Research Foundation seeks to promote the development of promising therapies for myelin disorders through innovative research projects. The Scientific Board of the ELA Foundation will favour collaborative and interdisciplinary projects. Pilot studies are also encouraged.

    Read about the call for proposals

     


     
    News from the Patients' Associations
     
    Eurordis 10 years on: continuing to meet the international challenges of patients' needs in Europe
     

    The European Organisation for Rare Diseases, now also known as "Rare Diseases Europe", has come a long way since its origins back in 1997, when it took its place in the European arena thanks to a European initiative by a coalition of 4 French associations: AFM-Téléthon (Muscular Dystrophy), VLM (Cystic Fibrosis), LNCC (Cancer League) and AIDES (AIDS Federation). Ten years on, in 2007, Eurordis now occupies a great deal more space on the Euro agenda, with a representation of more than 600 patient organisations from 33 countries including 22 Member States, a self-styled "voice for 30 million rare disease patients".

    Last week, Eurordis held an extensive 3-day event at the Institut Pasteur in Paris which examined contemporary RD patients’ issues and concerns from a Research perspective and endeavoured to seek actions and solutions for the future. This featured a European Workshop on "Gaining Access to RD Research Resources", with European and US representation; numerous RD patient organisation network meetings; a Membership Meeting jointly organised with the French RD Alliance; a press conference as well as a medley of satellite business meetings including the kick-off meeting of the Eurordis Task Force on Drug Information, Transparency and Access – DITA TF.

    European MEP Françoise Grossetête, well known among the RD community for her tireless work in support of orphan and paediatric drugs EU legislation, gave a moving speech at the 10th anniversary reception held in the Eiffel Tower, in which she described the difficulties encountered in her personal battle to help fast-track this RD legislation through the European Parliament.

    The Conference concluded with 2 workshops and a debate examining the future contribution of patient representatives to EU research projects, after which reports and recommendations for each workshop were drawn up. These aimed to provide some tangible conclusions resulting from the lively presentations and talks held at this landmark European crossroads of patients and experts involved in rare diseases.

    Click here to consult the slide presentations made at the Eurordis 10th anniversary European Workshop



     
    Patients' information leaflets on genetic testing by EuroGentest
     

    EuroGentest has published a series of 11 patient information leaflets on major topics in genetic disease and genetic testing designed to provide help and information for patients in their genetic research and contacts with genetic counsellors. The leaflets, which are published in English and currently undergoing translation into Polish, Romanian and Italian, and soon into all other EU languages, have been endorsed by patients' groups across Europe. Besides being fully downloadable by internet, the leaflets will also be publically available at genetic clinics in the EU as well as through patient groups and other relevant organisations.

    Organisers working on the project are quick to point out the necessity of these information leaflets which they believe stems from the lack of a truly comprehensive, standardised approach to genetic consultation, following the observation by patients of major discrepancies with regard to quality of information provided by genetic clinics across Europe. For example, patient interest groups unanimously voiced a concern that, although the benefits of genetic testing were generally clearly expressed, there was little or no mention of the risks involved.

    The 11 leaflets cover the following subjects:

    - Genetic Inheritance Patterns
    - Chromosome Problems
    - Genetic Testing
    - Information about your Genetic Appointment
    - Frequently Asked Questions for use when speaking to genetic specialists
    - A detailed Genetic Glossary

     


     
    Courses & Educational Initiatives
     
    European Summer School: Stem Cells & Regenerative Medicine
    Date: 14-21 September 2007
    Venue: Hydra, Greece

    This summer school will provide a critical analysis of contemporary issues in stem cell biology. During the in-depth, week-long programme, participants will attend lectures and workshops on:

    - The biology of stem cells - embryonic, fetal & adult systems
    - Plasticity, epigenetic regulation, signalling & niche
    - Clinical applications and clinical trials
    - Ethics and patents in stem cell research

    More details

    Advanced Course: Stem Cells and therapeutic applications
    Date: 8-22 November 2007
    Venue: Evry, France

    As part of its advanced training programme, Genopole is organising a course dedicated to stem cells and therapeutic applications. This advanced course is intended for researchers in biology, post-PhD students, and scientific directors already involved in stem cell research.

    More details

     


     
    What's on Where?
     
    Annual workshop 2007 - Organized by: Quebec Association of Genetic Counsellors (QAGC)
     
    Date: May 25, 2007
    Venue: Montreal, Quebec, Canada
    Contact this address for details

     
    Ethics Matters: 18th Canadian Bioethics Society Conference & 3rd International Conference on Clinical Ethics and Consultation
     
    Organized by the Canadian Bioethics Society
    Date: May 30-June 3, 2007
    Venue: Toronto, Ontario, Canada
    More details

     
    European Human Genetics Conference 2007
     
    Date: 16-19 June 2007
    Venue: Nice, France
    More details

     
    1-day Conference: Clinical Research for Rare Diseases: Opportunities, Challenges and Solutions
     
    Date: 5 September 2007
    Venue: Washington, DC, USA
    More details

     
    Rare Diseases Research: Building on Success - a European Conference
     
    Date: 13 September 2007
    Venue: Charlemagne building- Brussels, Belgium
    Web details to follow shortly

     
    4th Stem Cell Gene Therapy Conference
     
    Date: 13 September 2007
    Venue: Halkidiki, Thessaloniki, Greece
    More details

     
    EuroGentest Workshop on internal auditing for genetic testing laboratories
     
    Date: 20-21 September 2007
    Venue: Leuven, Belgium

    Registration is open for this event, which is EuroGentest's next workshop. The topic of the upcoming workshop will be internal audit for genetic testing laboratories. The content will be similar to that of the previous workshop on internal audit, the content will be mainly the same. EuroGentest will have general presentations, role play, video fragments and group discussions on how to prepare, execute and report internal audits. Registration deadline: 15 July 2007

    More details and to register now

     
    8th EPPOSI Partnering Workshop on Orphan Drugs
     
    Date: 18-19 October 2007
    Venue: Copenhagen
    More details

     
    Biology and clinical applications of cord blood cells
     
    Date: 19-21 October 2007
    Venue: Paris, France
    More details

     
    4th European Conference on Rare Diseases (ECRD 2007)
     
    Date: 27-28 November 2007
    Venue: Lisbon, Portugal
    NB: Registration is open. Deadline for abstract submission: 30 May 2007
    More details

     
    15th Annual Meeting, Int'l ALS/MND Associations Alliance & 18th ALS/MND Int'l Symposium
     
    Date: 1-3 December 2007
    Venue: Toronto, Canada
    More details

     


     
    Press & Publications
     
    Defending the Genetic Supermarket: The Law and Ethics of Selecting the Next Generation
     
    Author : Colin Gavaghan
    Publisher: Routledge-Cavendish 2007

    "The controversial topic of the technology of Pre-implantation Genetic Diagnosis, and the muddled approach to this subject adopted by the UK Parliament, is explored in detail in this volume. The author takes the viewpoint that the HFEA has taken insufficient notice to date of certain core ethical principles and makes the case for a much more ethically consistent and humane system than has been managed so far.

    Arguing that many of the fears and objections levied against Robert Nozick’s notion of the ‘Genetic Supermarket’ by disability activists, christian bioethicists and radical feminists, amongst others, are internally inconsistent, philosophically unsound or merely highly improbable, the author considers a number of individual policy decisions of the HFEA and addresses such questions as:

    - Can a case be made out for state involvement in such decisions?
    - Who stands to be harmed by a supermarket model?
    - Are any ethical principles or societal interests threatened by it?

    This book is an essential resource for law students of all levels and professionals working within or interested in medical and healthcare law and medical genetics".
    More details about this book

     
    Tic Talk : Living with Tourette Syndrome - A 9-year-old boy's story in his own words
     
    Author : Dylan Peters
    Publisher : Little Five Star
    ISBN 978-1-58985-051-4

    Nine-year-old Dylan Peters, describes Tourette syndrome: "your brain has a mission to annoy you". At the age of 4, when Dylan was diagnosed as having the syndrome, he made a wish to keep his disease a secret. However, over the following 5 years, whilst the tics became increasingly regular and severe, Dylan realised that this would not be possible. Dylan tells of how he came to accept the syndrome when he decided to explain his disease to his classmates.
    To find out more about this book


     
    European Commission- European Science and Technology Observatory
     
    Pharmacogenetics and Pharmacogenomics: State-of-the-Art and Potential Socio-Economic Impact in the EU
    Luxembourg - April 1, 2006
    More details

     
    Steps to Independence - Teaching Everyday Skills to Children with Special Needs, 4th Edition
     
    Authors: Bruce L. Baker, Ph.D., & Alan J. Brightman, Ph.D., with Jan B. Blacher, Ph.D., Louis J. Heifetz, Ph.D., Stephen R. Hinshaw, Ph.D., & Diane M. Murphy, R.N.
    Publisher: AFD Editions

    In this manual which mainly targets parents, the authors present early learning abilities and through recorded tables show how to help parents teach their own children afflicted with intellectual impairment, autism or developmental difficulties, everything possible that might help these children develop the highest possible level of autonomy in all areas of daily life.

    More 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: Kathy Beuzard-Edwards
    Contact Us
    Editorial Board: Ségolène Aymé, Catherine Berens, Helen Dolk, Anders Fasth, Edmund Jessop, Matthieu Levi-Strauss, Jordi Llinares-Garcia, Annie Olry, Jérôme Parisse-Brassens, Claire Scharf-Kroener, Janos Sandor, Arrigo Schieppati, Rumen Stefanov, John F. Ryan, Domenica Taruscio
    For more information on the Rare Diseases Task Force
    Orphanet - All rights reserved