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Final meeting of the Rare Disease Task Force covers many fronts...
...especially the EC Decision establishing the European Committee of Experts on Rare Diseases

Champagne corks were popped in honour of the final meeting of the European Commission’s Rare Disease Task Force (RDTF), which took place on 23 October. The European Commission Communication Rare Diseases: Europe’s Challenges, adopted in November 2008, states that “The Commission should be assisted by an EU Advisory Committee on Rare Diseases ... to advise on implementation of this Communication". This new Committee, which will be known as the European Committee of Experts on Rare Diseases, will effectively replace the present structure of the RDTF, although many of the existing experts are expected to carry over into the new organisation. As a legal entity, the new Committee will be able to make recommendations to the EU Member States (such as recommendations concerning national rare disease plans), as well as the EU Parliament, the European Medicines Agency, the Committee for Orphan Medicinal Products and the United Nations.

The European Committee of Experts on Rare Diseases will include one representative from each member state, four representatives from patient organisations, four representatives of the pharmaceutical industry, six representatives from former rare disease projects, and one representative from the European Centre for Disease Control, each of whom will have a three year mandate. Disappointment was voiced by some RDTF members that the European Medicines Agency will not have a representative in the new Committee; an EMEA representative was present at virtually every RDTF meeting since its creation. The Commission Decision establishing a European Union Committee of Experts on Rare Diseases is expected to be published in the Official Journal of the European Union shortly.

While the October RDTF meeting naturally devoted a good portion of time discussing the particularities of the new Committee, other topics also featured on the agenda, including the implementation of the Second Health Programme (the results of the 2009 calls); the European Reference Networks on Rare Diseases (the situation on the proposal for a Directive on Cross-Border Healthcare; the list of ongoing pilot projects; the declaration of common principles on Centres of Expertise and European Reference Networks for Rare Diseases (POLKA Project); and action points for the Working Group on Standards of Care); the progress report of the Classification and Codification of Rare Diseases; and the state of the play of the EUROPLAN project.
Consult the report of the 23 October 2009 RDTF meeting   (Article updated on 27 November 2009)

Spotlight on...
Patently controversial: licensing, genes, diagnostics and research
Do gene patents ultimately help or hinder diagnostics and research for rare disorders?

In mid-October, OrphaNews Europe spoke with Deborah Heine, creator of the Claire Altman Heine Foundation, a non-profit, publicly-supported charity created in memory of daughter Claire, who died of spinal muscular atrophy type 1 (SMA1) at the age of nine months. Spinal muscular atrophies represent 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. Around 95% of cases are caused by homozygous deletions in the SMN1 gene encoding the SMN (survival motor neuron) protein.

The Claire Altman Heine Foundation (CAHF) dedicates a large part of its energy and funding toward establishing pan-ethnic population carrier screening for SMA that would allow couples to know the risk of giving birth to an affected child and take an appropriate decision. This goal, however, is hindered by a co-exclusive license agreement for the SMN1 gene, which, Ms. Heine, a lawyer, says seriously hampers access to carrier screening and diagnostics for SMA. Ms. Heine contends that the licensing arrangement between the patent holder of the SMN1 gene and the licensee(s) is also negatively impacting other forms of potential research involving the SMN1 gene. A position paper available on the CAHF website acknowledges that it is not the patent itself that is causing the problem but “rather how the patent is being used and enforced, resulting in a barrier to clinical access for SMA carrier screening.” Presently, only two laboratories (in the USA) conduct carrier screening for SMA. No other laboratories or laboratory testing kit manufacturers have been granted licenses. The position paper delineates the detrimental effects of exclusivity in gene licensing for SMA screening and diagnostic testing:

  • Causes labs that might have offered SMA carrier screening to avoid offering these services thus limiting clinical access to testing
  • Results in a lack of competition and incentive to improve testing services
  • Eliminates competition for pricing
  • Leaves no opportunity for independent confirmation of a test result (i.e. second opinion or full gene sequencing when needed)
  • Dictates and limits clinical access to both physician and patient
  • Limits education of medical students and residents due to lack of exposure of patented material
  • Limits the ability to use multiplex arrays, gene chips and other emerging technologies
  • Hinders scientific and medical advancement of the field and diminishes accrual of knowledge about the molecular basis of the disease (by greatly reducing the number of laboratories with access to the gene)
  • Compromises quality assurance because the regular nationwide programs for proficiency testing (CAP/ACMG) are not interested in setting up these programs for a single customer

  • The complex issue of genetic diagnostic testing patents and licensing is fraught with contention. In March of this year, the United States Secretary’s Advisory Committee on Genetics, Health and Society (SACGHS) issued a call for comments on a comprehensive study entitled Public Consultation Draft Report on Gene Patents and Licensing Practices and Their Impact on Patient Access to Genetic Tests (see the 29 April 2009 issue of OrphaNews Europe for a summary of the contents of the draft paper). Last month the SACGHS held a task force meeting to discuss both the draft report and the comments culled during the public consultation period. An article appearing in GenomeWeb News reports that the five-year investigation based on studies, case files and the public comments received during the consultation period, has concluded that gene patents may not facilitate innovation, and in fact, may hinder innovation by restricting genetic test utilisation and rendering difficult the process of accessing information for a patented gene or using it for research purposes.

    The opinion submitted by the CAHF on the draft paper reflects the frustration and sense of injustice the current patenting and licensing system can incur. The CAHF opinion recounts the particularities of the patent for the SMN1 gene:

    In the case of SMA, the patent holder did not even bear the financial burden of the discovery, rather an advocacy group and patients and families suffering from the disease donated funds and tissue samples to a researcher who then patented her discovery and sold it. The cost of gene discovery was born by patients and families suffering from the disease (a group truly motivated for innovation) and the “rewards” of their investment are not returning to them. Instead, patients and families affected by SMA are at the mercy of the patent holder. This is the case in many gene patents (familiar example, Canavan Disease).

    Based on testimony such as this, the task force analysis of the report finds that “In the realm of therapeutics, strong arguments can be made that patents enable innovation, drive progress and serve an important role”. However, “In the realm of diagnostics, patent-enabled exclusivity primarily results in a narrowing of offerings to patients and physicians”.

    A presentation of the final draft report and recommendations from the Chair of the SACGHS Task Force on Gene Patents and Licensing Practices, James P. Evans, MD, includes two critical recommendations culled from the findings:

    The creation of an exemption from liability for infringement of patent claims on genes for anyone making, using, ordering, offering for sale, or selling a test developed under the patent for patient care purposes”; and

    The creation of an exemption from patent infringement liability for those who use patent-protected genes in the pursuit of research. Related health care and research entities also should be covered by this exemption.

    The task force also issued the recommendation to “discourage the seeking, the granting, and the invoking of simple association patent claims" and counsels the development of "mechanisms to promote voluntary adherence to the principles reflected in NIH’s Best Practices for the Licensing of Genomic Inventions; the Organisation for Economic Co-Operation and Development’s (OECD) Guidelines for Licensing of Genetic Inventions; the NIH Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-wide Association Studies; and In the Public Interest: Nine Points to Consider in Licensing University Technology".

    The recommendation goes on to advise that the US Secretary of Health and Human Services “should also advocate that professional organizations involved in intellectual property policy and practice in this area work together to build on those norms and practices as they relate to gene-based diagnostics by articulating more specific conditions under which exclusive licensing and nonexclusive licensing of uses relevant to genetic testing are appropriate. Professional societies should work cooperatively to forge consensus positions with respect to gene patenting and licensing policies”.

    Dr. Evans cites the public comment of a laboratory director who observes that “Patents on genes associated with rare diseases may discourage investment”.

    These observations and recommendations echo earlier findings by the European Society of Human Genetics (ESHG). As was reported in the 30 April 2008 issue of OrphaNews Europe, the ESHG last year issued a set of recommendations for genetic testing patenting and licensing that seeks to encourage fairness and ultimately improve service provision to patients. The recommendations limit patent attribution in certain areas of genetic testing by limiting the patentable subject matter. As with the SACGHS recommendations, the ESHG evokes the guidance issued by the Organisation for Economic Cooperation and Development, which discourage license exclusivity and promotes practical and financial access to licensing. The ESHG recommendations were published in the European Journal of Human Genetics. (Consult the PubMed abstract).

    The SACGHS task force recommendations are not unanimously endorsed, however. The Biotechnology Industry Organization (BIO), the world’s largest biotechnology organisation with more than 1,200 members in over 30 countries, qualified the proposed SACGHS policies as “over-reaching” and “restrictive”. The BIO strongly disagrees with the conclusions the task force drew from its findings, and in a published statement argues that the task force recommendations would “do more harm to patients than good, particularly the patients of tomorrow who are relying on biotech innovation to bring the promises of personalized medicine to reality”. In reference to rare disorder testing and research, the BIO statement observes that “…some of the Committee’s own findings and case studies show how patenting and exclusive licensing practices can, indeed, be necessary to foster the development of these valuable tests for patients, particularly those with rare disorders, and that they have other positive impacts – such as incentives to promote physician and patient education, broader insurance coverage, and improved compliance”.

    Furthermore, GenomeWeb News reported that a “particularly scathing critique” was made by Brian Stanton, a molecular oncologist and ad hoc member of the SACGHS task force who formerly served as Director of Policy for the NIH’s Office of Technology Transfer and as a Practice Specialist for the United States Patent and Trademark Office. In a letter of dissention, Stanton accused the draft report of being “based on flawed assumptions" and that "…the data demonstrates no evidence that intellectual property laws or licensing practices are the cause of general harm, a lack of technology development, or any systemic lack of public access to genetic testing," according to the GenomeWeb News report.
    Read the full article on patents and genetic diagnostic tests


    National & International Policy Developments
    Taiwan rare disease conference gathers players from the region and beyond to discuss national policies

    In early October, the International Conference of National Policies and Actions on Rare Diseases gathered key stakeholders from Asia as well as experts from Europe to review policies and practices for rare diseases. Participants from China, France, India, Korea, Malaysia, the Netherlands, the Philippines, Singapore, South Africa, Taiwan and Thailand met on the occasion of the tenth anniversary of the Taiwan Foundation for Rare Disorders (TFRD) and the country’s orphan drug act, to compare rare disease strategies and exchange experiences. Taiwan has two key legislative measures relating to rare disorders. The Genetic Health Law, which enforces reproductive health and protects maternal-child health, stipulates that the country will provide pre-gestational, prenatal, antepartum, perinatal, and postnatal health care. Strategies include monitoring laboratory quality control, providing education and medical subsidies, training professionals, research development, and strengthening networks. Taiwan’s newborn screening programme extends to 99% of newborns and covers eleven disorders. Taiwan also has a Rare Disease and Orphan Drug Act. Implemented in the year 2000, it was the fifth such legislation to be adopted worldwide, and offers support and assistance to patients with rare diseases who need medical treatment, encourages rare disease research, and raises public awareness. Taiwan defines a rare disease as having a prevalence of less than one in ten thousand, although prevalence alone is not sufficient. To receive an official definition, recognition must be received by the rare disorder and orphan drug committee or a central competent authority. Expenditure for rare disease medical care has steadily increased in Taiwan. Over 80 medicinal products and 40 special nutrient supplements have been reviewed, established, and announced. The Taiwanese government subsidises the Taiwan Foundation for Rare Disorders for certain advocacy actions, such as educational materials, training, conferences, and preventive measures. (Read more about the activities of the TFRD)

    During the conference, presentations were made on the rare disease policies of France (the first country to adopt a budgeted national plan specific for rare disease research, care and treatment), the Netherlands, South Korea, and Taiwan. The presentation on France discussed the experiences culled from the country’s four-year stint with a budgeted strategy specific to rare diseases. Next, the Netherlands weighed in with a discussion of their orphan medicines policies and the development over eight years ago of the Dutch Steering Committee for Orphan Drugs. The future steps of the Committee were explored, along with a comparison of the overlapping functions and roles of the committee and those of the Health Ministry. An exploration of the policies and practices for rare diseases in South Korea followed. South Korea has both governmental and private, non-profit mechanisms in place for rare disorders, including a subsidy for the medical expenses for rare diseases; a genetic and rare disease centre; a rare disease care centre and regional centre; three national reference centres; a newborn screening programme (six metabolic disorders and hereditary deafness); a non-profit orphan drug centre that supplies medical products for rare diseases; a national helpline; and an initiative to establish a national plan. Finally, Taiwan presented its current initiatives and future needs – including its educational and advocacy efforts, the national health insurance scheme, research, genetics, and budgeting. Taiwan has decided to allocate 2% of its tobacco tax revenues to rare disease prevention and management. The one-day event closed with a question and answer session and discussion of the elements comprising the various strategies – including prevalence, biobanks, centres of reference for rare disorders, and reimbursement issues.

    US rare disease clinical research network expands in its second phase

    Last month, the US National Institutes of Health announced $117 million funding for 19 “new and returning” research consortia under the second phase of the Rare Diseases Clinical Research Network (RDCRN). The Rare Diseases Clinical Research Consortia and a Data Management Coordinating Center will be funded for a five-year period for research exploring the natural history, epidemiology, diagnosis and treatment of over 95 rare disorders. In a press release, NIH Director Francis S. Collins, M.D. observed that the network has proven itself to be "…a catalyst for progress in meeting the challenge of rare diseases..." defining the progress accomplished by the network since its creation in 2003 as “important and impressive”. Over 5000 patients have been enrolled in 37 rare disease clinical studies since the RDCRN got under way. In the press release, NIH’s Office of Rare Diseases Research (ORDR) director Stephen C. Groft commented that "The network emphasizes collaboration not just among investigators from multiple research sites but between investigators and patient advocates as well." Indeed, each network consortium includes relevant patient advocacy groups as members and participants. In the first phase of the network, a voluntary patient registry was developed providing “ongoing contact with approximately 5,000 individuals from over 60 countries representing 42 diseases, alerting them when new studies are opened in the network or when ongoing studies expand to new sites”. Funding, scientific oversight and administrative support for the RDCRN are furnished by the ORDR along with seven NIH Institutes. The new consortia being funded are the Autonomic Rare Diseases Clinical Research Consortium; Brain Vascular Malformation Consortium; Dystonia Coalition; Hereditary Causes of Nephrolithaisis and Kidney Failure Consortium; Immune Disorders After Allogeneic HTC Consortium; Inherited Neuropathies Consortium; Lysosomal Disease Consortium; Nephrotic Syndrome Consortium; Primary Immune Deficiency Treatment Consortium; Sterol and Isoprenoid Diseases Consortium; Molecular and Epidemiologic Characterization of Salivary Gland Carcinomas Consortium; Porphyria Rare Disease Clinical Research Consortium; Spinocerebellar Ataxias Clinical Research Consortium; and the North America Mitochondrial Diseases Consortium. Continuing from the first phase of the RDCRN are the Angelman, Rett, and Prader-Willi Syndromes Consortium; the Consortium for Clinical Investigation of Neurologic Channelopathies; Genetic Disorders of Mucociliary Clearance Consortium; Urea Cycle Disorders Consortium; and the Vasculitis Clinical Research Consortium. The outgoing consortia are the Cholestatic Liver Disease Consortium; Rare Genetic Steroid Disorders Consortium; Bone Marrow Failure Consortium; Rare Lung Diseases Consortium; and the Rare Thrombotic Diseases Consortium. The RDCRN is making available web sites and/or other contact information for these groups, some of which are continuing research outside of the RDCRN network. The RDCRN website received over 3.4 million visits in 2008.

    Other European news
    EPPOSI’s tenth workshop produces recommendations for continuing progress in the rare disease field

    The European Platform for Patients’ Organisations, Science and Industry (EPPOSI) held another successful workshop designed to further rare disease therapy development via partnership and collaboration. This year marked the tenth workshop bringing together government representatives, clinicians, patient groups and industry members, and attendees also tipped their hats in celebration of the tenth anniversary of the adoption of EU Regulation EC 141/2000 on orphan medicinal products. This year’s themes addressed three diverse yet equally critical issues: the issue of funding in the midst of a global economic recession; building on existing policies and moving forward; and rare cancers. Held in the Federal Parliament of Belgium, in the presence of Her Royal Highness Princess Astrid of Belgium, the two-day EPPOSI workshop yielded several recommendations linked to the various topics addressed:

  • Additional targeted policy measures and incentives need to be identified to promote R&D in the field of rare diseases and orphan drugs
  • Doctors’ awareness and education needs to be raised in order to improve the chances for early diagnosis of rare diseases, and for enabling more research
  • Continuation of the orphan drug regulation 141/2000 got strong support as orphan drug development and availability could not rely on a free market to attract investments and drive innovation for rare diseases
  • European collaboration for the assessment of clinical added-value of orphan medicines was strongly supported and participants called for immediate creation of the Working Party at the EMEA
  • Orphan medicines should be conditionally reimbursed in Member States upon approval at EU level, subject to revision when more data become available, based on the revised report on the clinical added value
  • Rare cancers must continue to be included in public policies for rare diseases and orphan medicines
  • Transparency about pricing, budgets and total impact of orphan medicines needs to be improved
  • Priority needs to be given to setting up Centers of Expertise and European Reference Networks for diseases for which orphan drugs are approved, to speed up access and promote diagnostic and care standards

  • In a press release, Jean-Jacques Cassiman, EPPOSI Secretary-General and Chair of the Belgian Steering Committee for Rare Diseases and Orphan Drugs under the King Baudouin Foundation, remarked: “We cannot allow the economic crisis to take from our commitment to research or to negatively affect potentially life-changing policies in areas such as severe and rare diseases. There must be policy continuity in this area and continued investment in research to ensure the best quality healthcare for all European citizens.” The final report from the workshop has not been issued, but the speaker presentations from the event are available on the EPPOSI website.


    Ethical, Legal & Social Issues
    Who rules the patient associations? A French study suggests that groups with diverse stakeholders as leaders perform better
    A comparative study appearing in the review Sociology of Health & Illness took stock of the inner structure, functioning and resources of eight rare disease patient organisations, covering six different disorders in order to analyse the role stakeholder representation played. Specifically considering the relationship between decision-making and the diversity of stakeholders in leadership positions, the results suggest that those patient groups that have varied stakeholder representation – particularly in decision making roles – achieve better results. The author distinguishes two main types of organisation: ‘pluralistic’ groups that bring together a broad array of different stakeholders who are willing to work together and ‘monistic’ organisations in which a single category of stakeholders firmly takes the lead. The author reports that , “a key finding is that both the usual opposition between lay and expert and the reference to the diseases’ characteristics prove to be irrelevant to understanding these organisations. Rather, the composition of the leading group is crucial”. The study looked at French national groups for the diseases cystic fibrosis, fragile X syndrome, Wilson disease, mastocytosis, locked-in syndrome, and an especially infrequent syndrome that the author labelled the Very Rare Syndrome, in order to protect patient identity and confidentiality. Of some single-stakeholder led groups, the author observes that “These associations are a contrast to ‘pluralistic associations’ in many ways: the willingness to be supported is greater than that to engage in collective work with other groups, and especially with a scientific board; action is highly emotion-driven, as opposed to the collaboration-driven action of ‘pluralistic associations’, its temporal scope is strongly influenced both by past experience and the way the leaders picture an ideal future and tends to neglect the present or the near future; and a sudden ‘back to normalcy’ state is hoped for, which is considered a nonsense in ‘pluralistic associations’ ”. The author acknowledges the need for further study of this issue.
    Consult the PubMed abstract


    Orphanet News
    With support from Pfizer, the Orphanet Journal of Rare Diseases to waive publication fees for authors from low-income countries

    Earlier this year, Pfizer announced an agreement with BioMed Central to launch an Open Access Waiver Fund, supporting automatic waivers of publication fees for authors from low-income countries. Under this fund, authors submitting from any of 90 low-income countries should automatically be granted a full waiver of the article-processing charge. This waiver policy applies to manuscripts submitted to the Orphanet Journal of Rare Diseases. It is hoped that implementing the automatic country waivers fund across all of BioMed Central’s journals will help towards lifting the barrier between low-income countries and publishing high-quality research.

    New Texts
    Two new articles published in the European Journal of Human Genetics in association with Orphanet
    Menkes disease
    Coffin–Lowry syndrome

    New Orphanet Journal of Rare Diseases publication
    The Exstrophy-epispadias complex

    New Syndromes
    A new X-linked intellectual deficit syndrome with microcephaly, cortical malformation, and thin habitus
    X-linked intellectual deficit affects 1-2/1,000 males and accounts for approximately 10% of all intellectual deficit. The authors have ascertained a syndromic form of X-linked intellectual deficit segregating within a five-generation family with seven affected males. Prominent characteristics include mild to severe intellectual deficit, cortical malformation, microcephaly, seizures, thin build with distinct facial features including a long and thin face, epicanthic folds, almond-shaped eyes, upslanting palpebral fissures and micrognathia and behavioural problems. Carrier females have normal physical appearance and intelligence. This combination of features is unreported and distinct from Lujan-Fryns syndrome, Snyder-Robinson syndrome, and zinc finger DHHC domain-containing 9-associated intellectual deficit.
    Read the PubMed abstract

    Am J Med Genet ; 2469-2478 ; November 2009
    Neuropathy and bilateral striatal necrosis with SLC25A19 mutation at cause
    Four patients, aged 7-20 years, suffered from recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy. A pathogenic missense mutation in the SLC25A19 gene that encodes the mitochondrial thiamine pyrophosphate transporter was identified. An SLC25A19 mutation was previously reported in Amish congenital lethal microcephaly but the present phenotype is markedly different, with normal head circumference, normal early childhood development, age-appropriate cognitive skills, and normal urinary organic acid profile.
    Read the PubMed abstract

    Ann Neurol ; 419-424 ; September 2009
    Absence of pain with hyperhidrosis
    Congenital absence of pain perception is a rare phenotype. The authors report two unrelated adult individuals who have a previously unreported neuropathy consisting of congenital absence of pain with hyperhidrosis (CAPH). Both subjects had normal intelligence and productive lives despite failure to experience pain due to broken bones, severe cold or burns. Sweating was 3 to 8-fold greater than normal. Sural nerve biopsy showed that all types of myelinated and unmyelinated fibers were severely reduced.
    Read the PubMed abstract

    Pain ; Epub ahead of print ; 14 October 2009
    Hereditary hypotrichosis and recurrent skin vesicles with a DSC3 gene mutation
    The authors investigated a large family from Afghanistan in which four individuals are affected with hereditary hypotrichosis and the appearance of recurrent skin vesicle formation. All four affected individuals showed sparse and fragile hair on scalp, as well as absent eyebrows and eyelashes. Vesicles filled with thin, watery fluid were observed on the scalps and on most of the skin covering their bodies. A homozygous nonsense mutation in the desmocollin-3 (DSC3) gene was identified.
    Read the PubMed abstract

    Am J Hum Genet ; 515-520 ; October 2009

    New Genes

    Dravet syndrome: a functional null SCN1B mutation identified
    Dravet syndrome (also called severe myoclonic epilepsy of infancy) is one of the most severe forms of childhood epilepsy. Most patients have heterozygous mutations in SCN1A, encoding voltage-gated sodium channel Na(v)1.1 alpha subunits. Sodium channels are modulated by beta1 subunits, encoded by SCN1B, a gene also linked to epilepsy. Here the authors report the first patient with Dravet syndrome associated with a recessive mutation in SCN1B and propose that SCN1B is an autosomal recessive cause of Dravet syndrome through functional gene inactivation.
    Read the PubMed abstract

    To read more about "Dravet syndrome"

    J Neuroscience ; 10764-10778 ; 26 August 2009
    Joubert syndrome: OFD1 is mutated and interacts with LCA5-encoded lebercilin in X-linked form
    The authors ascertained a multi-generation Malaysian family with Joubert syndrome (JS). The presence of asymptomatic obligate carrier females suggested an X-linked recessive inheritance pattern. Affected males presented with intellectual deficit accompanied by postaxial polydactyly and retinitis pigmentosa. Brain MRIs showed the presence of a "molar tooth sign," which classifies this syndrome as classic JS with retinal involvement. Mutation analysis revealed a frameshift mutation in OFD1, previously associated with oral-facial-digital type 1 (OFD1) syndrome, a male-lethal X-linked dominant condition, and with X-linked recessive Simpson-Golabi-Behmel syndrome type 2 (SGBS2). The authors identified OFD1 as an interacting partner of the LCA5-encoded ciliary protein lebercilin and show that X-linked recessive mutations in OFD1 reduce, but do not eliminate, the interaction with lebercilin, whereas X-linked dominant OFD1 mutations completely abolish binding to lebercilin. These findings offer a molecular explanation for the phenotypic spectrum observed for OFD1 mutations; this spectrum now includes OFD1 syndrome, SGBS2, and JS.
    Read the PubMed abstract

    To read more about "Joubert syndrome"

    Am J Hum Genet ; 465-481 ; October 2009
    Progressive myoclonus epilepsy without renal failure: SCARB2 mutations identified
    Mutations in SCARB2 were recently described as causing action myoclonus renal failure syndrome (AMRF). The authors demonstrate that mutations in SCARB2 also account for unsolved cases of progressive myoclonus epilepsy (PME) without renal impairment, especially those resembling Unverricht-Lundborg disease (ULD).
    Read the PubMed abstract

    To read more about "Unverricht-Lundborg disease"

    Ann Neurol ; 532-536 ; October 2009
    Osteogenesis imperfecta: PPIB mutations cause severe form
    Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI).The authors now present two families with recessive OI caused by PPIB gene mutations. This result and the fact that CyPB is demonstrable independent of CRTAP and P3H1, along with reported decreased 3-prolyl hydroxylation due to deficiency of CRTAP lacking the catalytic hydroxylation domain and the known function of CyPB as a cis-trans isomerase, suggest that recessive OI is caused by a dysfunctional P3H1/CRTAP/CyPB complex rather than by the lack of 3-prolyl hydroxylation of a single proline residue in the alpha1 chains of collagen type I.
    Read the PubMed abstract

    To read more about "Osteogenesis imperfecta"

    Am J Hum Genet ; 521-527 ; October 2009
    Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1
    Absence epilepsies of childhood are heterogeneous with most cases following complex inheritance. Those cases with onset before 4 years of age represent a poorly studied subset. The authors screened 34 patients with early-onset absence epilepsy for mutations in SLC2A1, the gene encoding the GLUT1 glucose transporter. Mutations leading to reduced protein function were found in 12% of patients. Two mutations arose de novo, and two were familial. These findings suggest GLUT1 deficiency underlies a significant proportion of early-onset absence epilepsy, which has both genetic counselling and treatment implications because the ketogenic diet is effective in GLUT1 deficiency.
    Read the PubMed abstract

    To read more about "Epilepsy, childhood absence"

    Ann Neurol ; 415-419 ; September 2009
    Familial hemophagocytic lymphohistiocytosis type 5 is caused by mutations in Munc18-2 and impaired binding to syntaxin 11
    Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous autosomal-recessive disorder characterised by a severe hyperinflammatory phenotype. The authors found nine different mutations in STXBP2 in twelve FHL patients. STXBP2 encodes syntaxin binding protein 2 (Munc18-2), involved in the regulation of vesicle transport to the plasma membrane. The authors identified syntaxin 11, a SNARE protein mutated in FHL-4, as an interaction partner of STXBP2. This interaction is eliminated by the missense mutations found in the FHL-5 patients.
    Read the PubMed abstract

    To read more about "Familial hemophagocytic lymphohistiocytosis"

    Am J Hum Genet ; 482-492 ; October 2009
    Chronic granulomatous disease: a subgroup with mutations in p40 phox and defects in neutrophil NADPH oxidase activity
    Chronic granulomatous disease (CGD), an immunodeficiency with recurrent pyogenic infections and granulomatous inflammation, results from loss of phagocyte superoxide production by recessive mutations in any one of four genes encoding subunits of the phagocyte NADPH oxidase. The authors report the first case of autosomal recessive mutations in NCF4, the gene encoding p40(phox), in a boy who presented with granulomatous colitis. His neutrophils showed a substantial defect in intracellular superoxide production during phagocytosis, whereas extracellular release of superoxide elicited by phorbol ester or formyl-methionyl-leucyl-phenylalanine (fMLF) was unaffected.
    Read the PubMed abstract

    To read more about "Granulomatous disease, chronic"

    Blood ; 3309-3315 ; 8 October 2009

    Research in Action

    Fundamental Research
    ALS: intrathecal transplantation of human neural stem cells overexpressing VEGF show benefits in mice models
    Amyotrophic lateral sclerosis (ALS) is the most common adult onset motoneuron disease. The etiology and precise pathogenic mechanisms of the disease remain unknown, and there is no effective treatment. Vascular endothelial growth factor (VEGF) has recently been shown to exert direct neurotrophic and neuroprotective effects in animal models of ALS. Here the authors show that intrathecal transplantation of immortalised human neural stem cells (NSCs) overexpressing human VEGF gene significantly delayed disease onset and prolonged the survival of the SOD1G93A mouse model of ALS. At 4 weeks, post-transplantation grafted cells were found within the gray matter of the spinal cord. Furthermore, transplanted F3.VEGF cells that express neuronal phenotype (MAP2+) were found in the anterior horn of the spinal cord gray matter indicating that the transplanted human NSCs migrated into the gray matter, took the correct structural position, integrated into the spinal cord anterior horn and differentiated into motoneurons.
    Read the PubMed abstract

    To read more about "Amyotrophic lateral sclerosis"

    Gene Ther ; 1234-1244 ; October 2009
    Retinitis pigmentosa: retinal degeneration suppressed in Drosophila by stimulating endoplasmic reticulum-associated degradation
    Mutations in the rhodopsin gene that disrupt the encoded protein’s folding properties are a major cause of autosomal dominant retinitis pigmentosa (ADRP). This disease is faithfully modelled in Drosophila where similar mutations in the gene encoding rhodopsin-1 cause endoplasmic reticulum (ER) stress and dominantly trigger age-related retinal degeneration. The authors analysed the role of Drosophila genes homologous to the known yeast and animal regulators of the ER-associated degradation (ERAD) pathway, a process that reduces levels of misfolded proteins in the ER through proteasomal degradation. They found evidence that ERAD acts as a protective mechanism against retinal degeneration in the Drosophila model for ADRP. The results of this study suggest that manipulation of ERAD may serve as a powerful therapeutic strategy against a number of diseases associated with ER stress.
    Read the PubMed abstract

    To read more about "Retinitis pigmentosa"

    Proc Natl Acad Sci USA ; 17043-17048 ; 6 October 2009
    Congenital vision disorders: gene therapy successful in the case of red-green colour blindness in adult primates
    Red-green colour blindness, which results from the absence of either the long- or the middle- wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here the authors show that the addition of a third opsin in adult red-green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. This provides a positive outlook for the potential of gene therapy to cure adult vision disorders.
    Read the PubMed abstract

    Nature ; 784-787 ; 8 October 2009
    Spinal muscle atrophy: SMN mRNA induction results in an increase in SMN protein
    Spinal muscle atrophy (SMA) is an autosomal recessive neurodegenerative disease which is characterised by the loss of alpha motor neurons resulting in progressive muscle atrophy. Reduced amount of functional survival motor neuron (SMN) protein due to mutations or deletion in the SMN1 gene is the cause of SMA. A potential treatment strategy for SMA is to upregulate levels of SMN protein originating from the SMN2 gene compensating in part for the absence of functional SMN1 gene. The authors report a significant induction in SMN mRNA and protein following p38 activation by Anisomycin. They demonstrate that Anisomycin activation of p38 causes a rapid cytoplasmic accumulation of HuR, a RNA binding protein which binds to and stabilises the AU-rich element within the SMN transcript. The stabilisation of SMN mRNA, rather than transcriptional induction results in an increase in SMN protein.
    Read the PubMed abstract

    To read more about "Proximal spinal muscular atrophy"

    Hum Mol Genet ; 4035-4045 ; 1 November 2009
    Clinical Research
    A new method to search for clinical diagnosis of genetic diseases
    The differential diagnostic process attempts to identify candidate diseases that best explain a set of clinical features. This process can be complicated by the fact that the features can have varying degrees of specificity, as well as by the presence of features unrelated to the disease itself. Depending on the experience of the physician and the availability of laboratory tests, clinical abnormalities may be described in greater or lesser detail. The authors have adapted semantic similarity metrics to measure phenotypic similarity between queries and hereditary diseases annotated with the use of the Human Phenotype Ontology (HPO) and have developed a statistical model to assign p values to the resulting similarity scores, which can be used to rank the candidate diseases. They show that this approach outperforms simpler term-matching approaches that do not take the semantic interrelationships between terms into account. The advantage of the authors’ approach was greater for queries containing phenotypic noise or imprecise clinical descriptions. The semantic network defined by the HPO can be used to refine the differential diagnosis by suggesting clinical features that, if present, best differentiate among the candidate diagnoses. The authors have implemented their methods in a freely available web application for the field of human Mendelian disorders.
    Read the PubMed abstract

    Am J Hum Genet ; 457-464 ; October 2009
    Robinow syndrome and brachydactyly type B: a gradient of ROR2 protein stability and membrane localisation confers phenotype
    Mutations in ROR2 cause dominant brachydactyly type B (BDB1) or recessive Robinow syndrome (RRS), each characterised by a distinct combination of phenotypic features. The authors here report a novel nonsense mutation in ROR2 causing intracellular protein truncation in a patient exhibiting features of RRS in conjunction with severe recessive brachydactyly. To investigate the apparent discrepancy in phenotypic outcome, the authors analysed ROR2 protein stability and distribution in stably transfected cell lines expressing exact copies of several human RRS and BDB1 intracellular mutations and propose a model in which the RRS versus the BDB1 phenotype is determined by the relative degree of protein retention/degradation and the amount of mutant protein reaching the plasma membrane.
    Read the PubMed abstract

    To read more about "Robinow syndrome"
    To read more about "Brachydactyly, type B"

    Hum Mol Genet ; 4013-4021 ; 1 November 2009
    Ehlers-Danlos syndrome: homozygosity for a null allele of COL3A1 results in recessive form of the disease
    So far, mutations in the human COL3A1 gene have been associated with the predominantly inherited Ehlers-Danlos syndrome (EDS), vascular type. Genotype-phenotype correlation perspectives collapsed, as haploinsufficiency, which was long suggested to confer a milder or unrecognised phenotype, was reported in four patients with a phenotype similar to that of vascular EDS. Here, the authors present a case of recessive EDS in a young consanguineous girl of healthy parents and provides evidence of a stochastic effect of COL3A1 haploinsufficiency in humans, which could be explained by the relation between nonsense-mediated mRNA decay efficiency and the resulting dominant-negative effect depending on the position of the mutation and/or modifying factors. This opens up new perspectives for the understanding of COL3A1 genotype-phenotype correlations.
    Read the PubMed abstract

    To read more about "Ehlers-Danlos syndrome"

    Eur J Hum Genet ; 1411-1416 ; November 2009
    Database for Birt-Hogg-Dubé syndrome gene freely available via the Leiden Open Variation Database
    A new mutation database with comprehensive sequence variation data for FLCN, the gene associated with Birt-Hogg-Dubé syndrome, is freely available online via the Leiden Open (source) Variation Database. Available to all, and officially recognised by the Human Genome Variation Society, the FLCN data is curated by Dr Derek Lim, a Clinical Research Fellow at Birmingham University, UK, and has been developed with the European BHD Consortium. The database contains both published and novel unpublished data and submissions are encouraged. An article recently published in Human Mutation journal provides further details.
    Consult the PubMed abstract

    Gene Therapy
    Limb-girdle muscular dystrophy type 2D: gene therapy restores alpha-sarcoglycan and associated proteins
    alpha-Sarcoglycan deficiency results in a severe form of muscular dystrophy (limb-girdle muscular dystrophy type 2D [LGMD2D]) without treatment. Gene replacement represents a strategy for correcting the underlying defect. Questions related to this approach were addressed in this clinical trial, particularly the need for immunotherapy and persistence of gene expression. A double-blind, randomized controlled trial using rAAV1.tMCK.hSGCA injected into the extensor digitorum brevis muscle was conducted. A 3-day course of methylprednisolone accompanied gene transfer without further immune suppression. SGCA gene expression increased 4-5-fold over control sides when examined at 6 weeks (2 subjects) and 3 months (1 subject). The full sarcoglycan complex was restored in all subjects, and muscle fibre size was increased in the 3-month subject.
    Read the PubMed abstract

    To read more about "Muscular dystrophy, limb-girdle, autosomal recessive, type 2D"

    Ann Neurol ; 290-297 ; September 2009
    Leber congenital amaurosis: successful age-dependent effects of RPE65 gene therapy trial in twelve patients
    The authors assessed the retinal and visual function in 12 patients (aged 8-44 years) with RPE65-associated Leber congenital amaurosis given one subretinal injection of adeno-associated virus (AAV) containing a gene encoding a protein needed for the isomerohydrolase activity of the retinal pigment epithelium in the worst eye at low, medium, or high dose for up to two years. AAV2-hRPE65v2 was well tolerated and all patients showed sustained improvement in subjective and objective measurements of vision. Patients had at least a 2 log unit increase in pupillary light responses, and an 8-year-old child had nearly the same level of light sensitivity as that in age-matched normal-sighted individuals. The greatest improvement was noted in children, all of whom gained ambulatory vision. The safety, extent, and stability of improvement in vision in all patients support the use of AAV-mediated gene therapy for treatment of inherited retinal diseases, with early intervention resulting in the best potential gain.
    Read the PubMed abstract

    To read more about "Leber amaurosis, congenital"

    Lancet ; 1597-1605 ; 7 November 2009
    Diagnostic Approaches
    Fragile X syndrome incidence via newborn screening for methylated FMR1 DNA
    Fragile X syndrome (FXS) results from a CGG-repeat expansion that triggers hypermethylation and silencing of the FMR1 gene. FXS is referred to as the most common form of inherited intellectual disability, yet its true incidence has never been measured directly by large population screening. Here, the authors developed an inexpensive and high-throughput assay to quantitatively assess FMR1 methylation in DNA isolated from the dried blood spots of 36,124 deidentified newborn males. The assay can also detect excess FMR1 methylation in 82% of females with full mutations, although the methylation did not correlate with intellectual disability. With amelogenin PCR used for detecting the presence of a Y chromosome, this assay can also detect males with Klinefelter syndrome (KS). The authors identified 64 males with FMR1 methylation and, after confirmatory testing, found seven to have full-mutation FXS and 57 to have KS. Because the precise incidence of KS is known, the observed KS incidence was used as a sentinel to assess ascertainment quality and showed that the KS incidence of 1 in 633 newborn males was not significantly different from the literature incidence of 1 in 576. The seven FXS males revealed an FXS incidence in males of 1 in 5161, consistent with some earlier indirect estimates.
    Read the PubMed abstract

    To read more about "Fragile X syndrome"
    To read more about "Klinefelter syndrome"

    Am J Hum Genet ; 503-514 ; October 2009
    A new diagnostic workflow for patients with intellectual deficit and/or multiple congenital abnormalities: test arrays first
    High-density single-nucleotide polymorphism (SNP) genotyping technology enables extensive genotyping as well as the detection of increasingly smaller chromosomal aberrations. In this study, the authors assess molecular karyotyping as first-round analysis of patients with intellectual deficit and/or multiple congenital abnormalities (ID/MCA) using different commercially available SNP array platforms to detect copy number variants (CNVs) in 318 patients with unexplained ID/MCA. They found abnormalities in 22.6% of the patients, including six CNVs that overlap known microdeletion/duplication syndromes, eight CNVs that overlap recently described syndromes, 63 potentially pathogenic CNVs (in 52 patients), four large segments of homozygosity and two mosaic trisomies for an entire chromosome. This study shows that high-density SNP array analysis reveals a much higher diagnostic yield as that of conventional karyotyping. SNP arrays have the potential to detect CNVs, mosaics, uniparental disomies and loss of heterozygosity in one experiment.
    Read the PubMed abstract

    Eur J Hum Genet ; 1394-1402 ; November 2009
    Lysosomal storage disorders: raising awareness of musculoskeletal manifestations to improve early diagnosis
    Lysosomal storage disorders (LSDs), a heterogeneous group of inborn metabolic disorders, are far more common than most doctors presume. Although patients with a severe LSD subtype are often readily diagnosed, the more attenuated subtypes are frequently missed or diagnosis is significantly delayed. The presenting manifestations often involve the bones and/or joints and therefore these patients are frequently under specialist care by (paediatric) rheumatologists, receiving inadequate treatment. Since effective disease-specific treatments, including enzyme replacement therapy and stem cell transplantation, have become available for certain LSDs and timely initiation of these treatments is necessary to prevent the development of severe, disabling and irreversible manifestations, early diagnosis has become essential. The challenge is to raise awareness for better recognition of the presenting signs and symptoms of LSDs by all doctors who may encounter these patients, including rheumatologists.
    Read the PubMed abstract

    To read more about "Lysosomal storage disease with skeletal involvement"

    Ann Rheum Dis ; 1659-1665 ; November 2009

    Patient Management and Therapy

    Myotonic dystrophy type 1: preimplantation genetic diagnosis works well
    Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis for patients at risk of transmitting an inherited disease such as myotonic dystrophy type 1(DM1) to their offspring. In this paper, the clinical application of preimplantation diagnosis for DM1 is described in a large cohort of risk couples. PGD could be offered to all 78 couples opting for PGD regardless of the triplet repeat size. The incidence of major complications was minimised following a careful assessment in affected DM1 females anticipating possible cardiological, obstetrical and anaesthetical problems. A live-birth delivery rate per cycle with oocyte retrieval of 20% was the outcome. Forty-eight of the 49 children born are in good health and have normal psychomotor development.
    Read the PubMed abstract

    To read more about "Steinert myotonic dystrophy"

    Eur J Hum Genet ; 1403-1410 ; November 2009
    Polycystic liver disease: lanreotide reduces volume
    Therapy for polycystic liver is invasive, expensive, and has disappointing long-term results. Treatment with somatostatin analogues slowed kidney growth in patients with polycystic kidney disease (PKD) and reduced liver and kidney volume in a PKD rodent model. The authors evaluated the effects of lanreotide, a somatostatin analogue, in patients with polycystic liver because of autosomal-dominant PKD or autosomal-dominant polycystic liver disease. In a randomised, double-blind, placebo-controlled trial, 54 patients with polycystic liver were randomly assigned to receive lanreotide (120 mg) or placebo, administered every 28 days for 24 weeks. In patients with polycystic liver, six months of treatment with lanreotide reduced liver volume.
    Read the PubMed abstract

    To read more about "Polycystic liver disease"

    Gastroenterology ; 1661-1668 ; November 2009
    Still disease: anakinra administered in a patient during pregnancy with no negative consequence for foetus
    Adult-onset Still disease is a rare rheumatic condition. Its main feature is the combination of symptoms, such as fever higher than 39°, cutaneous rash during fever peaks, joint or muscle pain, lymph node hypertrophy, increase of white blood cells (especially polymorphonuclear neutrophils) and abnormalities of liver metabolism. During pregnancy, women present an elevated risk of premature delivery and intra-uterine growth delays. Anakinra, an interleukin 1 receptor antagonist allows for symptom reduction with rare side effects. The authors report a pregnancy followed by breastfeeding in a patient taking anakinra, with no negative effect for the offspring.
    Read the PubMed abstract

    To read more about "Still's disease, adult onset"

    Ann Rheum Dis ; 1794-1795 ; November 2009

    Orphan Drugs
    Over one hundred orphan medicinal products designated by the COMP so far this year...

    For the first time ever, the number of medicinal products receiving a positive opinion for orphan designation from the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency in a given year has climbed over one hundred. And we are still only in November! The COMP came close in 2007, with a total of 97 products receiving orphan designation in that year. At the November 2009 COMP meeting, fourteen positive opinions were issued for the treatment of:
    - oesophagus carcinoma
    - systemic-onset juvenile idiopathic arthritis
    - Huntington disease
    - perinatal asphyxia
    - malaria
    - pancreatic cancer
    - pneumonia caused by serotype O1 Pseudomonas aeruginosa
    - idiopathic pulmonary fibrosis
    - hyperphenylalaninaemia
    - glioma
    - amyotrophic lateral sclerosis
    - Netherton syndrome
    - congenital lymphatic malformations
    - chronic lymphocytic leukaemia

    Meanwhile, during the October 2009 COMP meeting, nine positive opinions were issued for the treatment of:
    - naevoid basal cell carcinoma syndrome (Gorlin syndrome)
    - sickle cell disease
    - hepatocellular carcinoma
    - ovarian cancer (two products)
    - neuroblastoma
    - acute myeloid leukaemia
    - acute lymphoblastic leukaemia
    - chronic lymphocytic leukaemia

    Consult the European Register of Designated Orphan Medicinal Products
    Consult the Orphanet list of orphan drugs authorised for marketing in Europe

    Orphan medicinal products dominate the 2009 Prix Galien USA winners
    The 2009 Prix Galien USA winners are dominated by orphan medicinal products. Amongst the 21 candidates, Novartis Oncology’s orphan product Gleevec (marketed as Glivec in Europe) won the Best Pharmaceutical Product. Two other orphan products were the winners in the category of Best Biotechnology Product: Nplate, a thrombopoietin receptor agonist used in the treatment of thrombocytopenic purpura, produced by Amgen, and orphan drug Promacta (GlaxoSmithKline), used for the treatment of thrombocytopenia. The Prix Galien originated in France as way of promoting innovation in pharmaceutical research and honouring innovative biopharmaceutical drugs and devices “that have made a deep impact on the quality of human life”. It has since been inaugurated across Europe and Canada and is now considered the most prestigious award of its kind in 11 countries. The USA Prix Galien committee includes seven Nobel Laureates.

    Partnersearch, Job Opportunities
    European Neuro Muscular Centre seeks Research Director
    The European Neuro Muscular Centre (ENMC) is a platform of international neuromuscular patient organisations, whose main scope is to facilitate communication among scientists, clinicians and persons affected by neuromuscular diseases, through the organisation of international workshops. The ENMC is a partner in collaborative activities, such as the EU funded Network of Excellence Treat-NMD. To guide and develop ENMC´s scientific activities, ENMC is seeking candidates for the position of ENMC Research Director. Duties will include chairing the research committee and guide the assessment of workshop applications; supporting the Executive Committee in the definition and implementation of the ENMC’s scientific policy and pro-actively support the scientific activities administered by the ENMC office; and representing ENMC and supporting its positioning in the neuromuscular community, also favouring its involvement in new opportunities. Application deadline: 15 December 2009
    For further details


    News from the Patients' Associations
    Bellisimo! Italy’s national rare disease organisation celebrates ten years of activity

    This summer the 10th anniversary of the Italian national Alliance of rare disease patient organisations, Federazione Italiana Malattie Rare (UNIAMO) took place in Venice. Founded in Rome in 1999 by a small group of associations, UNIAMO today includes 77 patient organisations, representing more then 600 different rare diseases. Over the past ten years, UNIAMO has fought patient isolation and has participated in the drafting of a proposal to support patients with rare disorders. The organisation has also promoted training courses for health professionals and encouraged patient empowerment via workshops on health and social regulation. UNIAMO disseminates information and organises public awareness-raising activities at the national and international level. During its first 10 years of activity, UNIAMO has emerged from a culture of need, incapacity and assistance into one of collaboration, expertise and resources. The celebration of UNIAMO marks an important step in the Italian field of public health care and assistance. During the anniversary conference that took place in Venice, a document on a strategic alliance was agreed to and signed by scientific entities, professional groups, and industry. This document outlines the commitment of physicians to better knowledge of the problems of rare disease patients and their families and of their related needs, as well as a commitment to research activities and to orphan drug development and distribution. The agreement was signed in the presence of the Hon. Francesca Martini, State Secretary to Welfare, who emphasised the importance of the strategic alliance between the associations, defending the rights of persons affected by rare disorders, the professional categories of general practitioners and paediatricians, related scientific bodies, the biopharmaceutical industry, and government. In Italy, pay exemption for health services included in the Essential Assistance Levels (LEA) exist for 583 defined diseases and/or disease groups. Still, many rare disorders in Italy are not included under LEA, with dramatic consequences to patients. During the conference, notice was given that within the coming year the government shall extend LEA to 109 more rare diseases.


    Courses & Educational Initiatives
    EuroGentest Workshop: Accreditation for Genetic Testing Laboratories According to ISO 15189
    This EuroGentest workshop taking place from 14-15 January 2010 in Birmingham, UK, will compare and share experiences of implementing and living with quality systems. Effective ways to move towards accreditation according ISO 15189, how to fulfill ISO 15189 requirements, to improve quality assurance, and common deficiencies in a QMS will be discussed. The workshop will be very interactive, including small group work, discussing cases and presentations of experts.
    For further information


    What's on Where?

    International Conference on Myasthenia
    Date: 1-2 December 2009
    Venue: Paris, France

    The conference will bring together research scientists and clinicians from around the world who specialise in myasthenia, to review the latest developments, exchange experiences and ideas, and broaden knowledge and understanding of this rare disease. A session dedicated to the interaction between clinicians, scientists, and patient associations is also scheduled.
    For further details

    Meeting of the International Society of Neonatal Screening and Latin American Society of Inborn Errors of Metabolism
    Date: 6-9 December 2009
    Venue: Cancun, Mexico

    For the first time the International Society of Neonatal Screening and the Latin American Society of Inborn Errors of Metabolism join forces to host this academic event aimed to foster the interchange of new ideas and experiences in the fields of inborn metabolic diseases and neonatal screening.
    For further details

    2010 Neuromuscular Disorders Conference: Toward a Better Future
    Date: 26-27 February 2010
    Venue: Sydney, Australia

    Featuring a stimulating and progressive programme disseminating the most recent research in the field of neuromuscular conditions, this conference will provide an exciting poster session where up and coming researchers will have an opportunity to present their research to the neuromuscular community.
    For further details

    2nd Pan-European Conference on Haemoglobinopathies
    Date: 13-14 March 2010
    Venue: Berlin, Germany

    This conference aims to further strengthen the national and regional support networks for thalassaemia patients in Europe, and increase awareness among European medical professionals and national health authorities of the disorder, its proper management and prevention.
    For further details

    6th International Conference on Rare Diseases and Orphan Drugs
    Date: 18-20 March 2010
    Venue: Buenos Aires, Argentina

    The 6th International Conference on Rare Diseases and Orphan Drugs (ICORD 2010) for the first time will be convened in the southern hemisphere in agreement with its aim of globalisation of rare disease research and orphan products development activities.
    For further details

    ASA-EHA Conference: Innovative Therapies for Red Cell and Iron Related Disorders
    Date: 16-18 April 2010
    Venue: Cascais, Portugal

    Sessions include:Hematopoietic stem cell therapies; molecular switching in erythroid differentiation; gene therapy; iron regulatory pathway for therapies; innovative therapies for red cell disorders, and more.
    For further details

    18th International Workshop on Vascular Anomalies
    Date: 21-24 April 2010
    Venue: Brussels, Belgium

    Topics will include clinical and basic research in the pathophysiology, diagnosis and management of vascular anomalies, as well as the psychosocial challenges faced by the patients.
    For further details

    Birt-Hogg-Dubé Symposium 2010
    Date: 22 April 2010
    Venue: Washington, DC USA

    A symposium for reviewing the latest developments for Birt-Hogg-Dubé syndrome.
    For further details

    5th European Conference on Rare Diseases 2010
    Date: 13-15 May 2010
    Venue: Crakow, Poland

    Details will be available soon.

    22nd Annual Meeting of the European Academy of Childhood Disability
    Date: 27-29 May 2010
    Venue: Brussels, Belgium
    This year’s event - Measures of Progress – Evaluating management outcome in childhood disability - will update and clarify the multidimensional model of disablement specifically applied to management of children with neurodevelopmental disability. Emphasis is on the need for reliable measurement of management outcomes through new findings, from functional imaging to quality of life assessment. Deadline for abstract submission: 1 February 2010
    For further details

    First International Workshop on Oesophageal Atresia
    Date: 27-28 May 2010
    Venue: Lille, France

    Amongst the topics covered will be: molecular embryology of the foregut; environmental factors in the etiology of esophageal atresia; genetic factors in isolated and syndromic esophageal atresia; ultrasound and MRI prenatal diagnosis of OA: impact on management; Outcomes of esophageal atresia beyond childhood; multidisciplinary clinics: how to improve the follow-up of the patients?; and family support groups: an essential contribution to follow-up care.
    For further details

    European Human Genetics Conference 2010
    Date: 12-15 June 2010
    Venue: Gothenburg, Sweden

    In conjunction with the European Meeting on Psychosocial Aspects of Genetics. Deadline for Abstract Submission: 19 February 2010.
    For further details

    14th International Conference on Behçet Disease
    Date: 8-10 July 2010
    Venue: London, England

    Presenting new developments in basic and clinical science to bear on the specific issues of Behçet Disease (BD). Topics to be covered will include immunology of BD, vasculitis in BD, genetic basis of BD, regional inflammation and paediatric BD. The programme will also include debates on topics of current interest or controversy.
    For further details

    Men 2010: 12th International Workshop on Multiple Endocrine Neoplasia
    Date: 16-18 September 2010
    Venue: Viareggio, Italy

    This two-day meeting will provide a forum for educating basic and clinical investigators on the most recent advances in the area of hereditary endocrine tumours.
    For further details


    Press & Publications

    Two new papers from the Genetic Alliance
    The review Genetic Testing and Molecular Biomarkers recently published two articles by the leaders of the non-profit health advocacy organisation Genetic Alliance. Collaboration: The Foundation for Success in Rare Disease Genetic Test Development describes the success of the US Collaboration Education and Test Translation (CETT) programme, which was established in 2006 and is supported by the NIH Office of Rare Diseases Research (ORDR), to aid in the translation of new genetic tests from research to clinical laboratories. The article states that “more rare disease tests are available in clinical laboratories, and more diseases have tests available as a result of the CETT program”. Indeed, “the CETT program has approved 35 applications and facilitated translation of genetic tests for 93 genes related to 68 genetic conditions, including arrhythmogenic right ventricular cardiomyopathy (ARVC), pseudoxanthoma elasticum (PXE), Joubert syndrome, Niemann Pick type A and B, and mucopolysaccharidosis type VI (MPS VI).” The authors point out that the “program’s systems level approach, with intensive and formal collaboration by all key stakeholders, is essential in the age of molecular diagnostics, particularly as we move into the era of personalized medicine when networked collaboration will accelerate translation”. In the second article, entitled Transparency, Openness, and Genetic Testing, the authors echo an earlier call for a genetic test registry as well as an “infrastructure that ensures tests are accurate, reliable, and safe”. The authors assert that a registry for genetic tests would “benefit all stakeholders, including researchers, industry, payers, and especially the federal agencies who are tasked to oversee various aspects of the genetic testing system”. The article goes on to describe what such a registry should include, how it should be operated, and by whom. The authors define the development of a registry for genetic tests as a “grand opportunity” to create a “forward looking, forward thinking, comprehensive product.” Such a mechanism for transparency could be especially useful to the rare disease community.
    Consult the first PubMed abstract
    Consult the second PubMed abstract


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