Establishment of the first WHO international genetic reference panel for Prader Willi and Angelman syndromes.
Summary of "Establishment of the first WHO international genetic reference panel for Prader Willi and Angelman syndromes."
Prader Willi and Angelman syndromes are clinically distinct genetic disorders both mapping to chromosome region 15q11-q13, which are caused by a loss of function of paternally or maternally inherited genes in the region, respectively. With clinical diagnosis often being difficult, particularly in infancy, confirmatory genetic diagnosis is essential to enable clinical intervention. However, the latter is challenged by the complex genetics behind both disorders and the unmet need for characterised reference materials to aid accurate molecular diagnosis. With this in mind, a panel of six genotyping reference materials for Prader Willi and Angelman syndromes was developed, which should be stable for many years and available to all diagnostic laboratories. The panel comprises three Prader Willi syndrome materials (two with different paternal deletions, and one with maternal uniparental disomy (UPD)) and three Angelman syndrome materials (one with a maternal deletion, one with paternal UPD or an epigenetic imprinting centre defect, and one with a UBE3A point mutation). Genomic DNA was bulk-extracted from Epstein-Barr virus-transformed lymphoblastoid cell lines established from consenting patients, and freeze-dried as aliquots in glass ampoules. In total, 37 laboratories from 26 countries participated in a collaborative study to assess the suitability of the panel. Participants evaluated the blinded, triplicate materials using their routine diagnostic methods against in-house controls or externally sourced uncertified reference materials. The panel was established by the Expert Committee on Biological Standardization of the World Health Organization as the first International Genetic Reference Panel for Prader Willi and Angelman syndromes.European Journal of Human Genetics advance online publication, 18 May 2011; doi:10.1038/ejhg.2011.59.
Affiliation
National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Herts, UK.
Journal Details
This article was published in the following journal.
Name: European journal of human genetics : EJHG
ISSN: 1476-5438
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21587322
- DOI: http://dx.doi.org/10.1038/ejhg.2011.59
Medical and Biotech [MESH] Definitions
Prader-willi Syndrome
An autosomal dominant disorder caused by deletion of the proximal long arm of the paternal chromosome 15 (15q11-q13) or by inheritance of both of the pair of chromosomes 15 from the mother (UNIPARENTAL DISOMY) which are imprinted (GENETIC IMPRINTING) and hence silenced. Clinical manifestations include MENTAL RETARDATION; MUSCULAR HYPOTONIA; HYPERPHAGIA; OBESITY; short stature; HYPOGONADISM; STRABISMUS; and HYPERSOMNOLENCE. (Menkes, Textbook of Child Neurology, 5th ed, p229)
International Normalized Ratio
System established by the World Health Organization and the International Committee on Thrombosis and Hemostasis for monitoring and reporting blood coagulation tests. Under this system, results are standardized using the International Sensitivity Index for the particular test reagent/instrument combination used.
United Nations
An international organization whose members include most of the sovereign nations of the world with headquarters in New York City. The primary objectives of the organization are to maintain peace and security and to achieve international cooperation in solving international economic, social, cultural, or humanitarian problems.
International Agencies
International organizations which provide health-related or other cooperative services.
Recombination, Genetic
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
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