Prader-Willi and Angelman syndromes: Sister imprinted disorders
- 1 January 2000
- journal article
- research article
- Published by Wiley in American Journal of Medical Genetics
- Vol. 97 (2) , 136-146
- https://doi.org/10.1002/1096-8628(200022)97:2<136::aid-ajmg5>3.0.co;2-v
Abstract
Prader‐Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct complex disorders mapped to chromosome 15q11‐q13. They both have characteristic neurologic, developmental, and behavioral phenotypes plus other structural and functional abnormalities. However, the cognitive and neurologic impairment is more severe in AS, including seizures and ataxia. The behavioral and endocrine disorders are more severe in PWS, including obsessive–compulsive symptoms and hypothalamic insufficiency. Both disorders can result from microdeletion, uniparental disomy, or an imprinting center defect in 15q11‐q13, although the abnormality is on the paternally derived chromosome 15 for PWS and the maternally derived 15 for AS because of genomic imprinting. Although the same gene may control imprinting for both disorders, the gene(s) causing their phenotypes differ. AS results from underexpression of a single gene, UBE3A, which codes for E6‐AP, a protein that functions to transfer small ubiquitin molecules to certain target proteins, to enable their degradation. The genes responsible for PWS are not determined, although several maternally imprinted genes in 15q11‐q13 are known. The most likely candidate is SNRPN, which codes for a small nuclear ribonucleoprotein, a ribosome‐associated protein that controls gene splicing and thus synthesis of critical proteins in the brain. Animal models exist for both disorders. The genetic relationship between PWS and AS makes them unique and potentially highly instructive disorders that contribute substantially to the population burden of cognitive impairment. Am. J. Med. Genet. (Semin. Med. Genet.) 97:136–146, 2000Keywords
This publication has 88 references indexed in Scilit:
- Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome patients with an imprinting mutationAmerican Journal of Medical Genetics, 1997
- De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndromeNature Genetics, 1997
- Angelman syndrome in adulthoodAmerican Journal of Medical Genetics, 1996
- Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN geneNature Genetics, 1996
- Inherited microdeletions in the Angelman and Prader–Willi syndromes define an imprinting centre on human chromosome 15Nature Genetics, 1995
- Protein ubiquitination involving an E1–E2–E3 enzyme ubiquitin thioester cascadeNature, 1995
- Angelman syndrome due to paternal uniparental disomy of chromosome 15: A milder phenotype?American Journal of Medical Genetics, 1994
- Genomic imprinting and uniparental disomy in Angelman and Prader‐Willi syndromes: A reviewAmerican Journal of Medical Genetics, 1993
- Angelman Syndrome: Clinical ProfileJournal of Child Neurology, 1992
- Neuropsychological capacity of prader-willi children: General and specific aspects of impairmentApplied Research in Mental Retardation, 1986