Molecular genetic analysis of Prader-Willi and Angelman syndromes
- Oulu Univ. Central Hospital (Finland)
Angelman (AS) and Prader-Willi (PWS) syndromes are caused by the loss of either maternal (AS) or paternal (PWS) contributions to chromosome 15q11-q13 region, which is subject to genomic imprinting. DNA methylation has been postulated to play a crucial role in genomic imprinting and the diagnostic test used is based on the differential parental methylation of 15q11-q13. We report here the DNA studies of 39 classical PWS and 12 AS patients. For DNA polymorphism and dosage studies we used nine genomic probes and five microsatellite markers specific for chromosome 15. To study the methylation patterns the probes DN34 (D15S9) and PW71 (D15S63), which show a parental-specific DNA methylation imprint, were used. Among the PWS patients, 29 (77%) cases with a deletion belonging to four different size classes and 9 (23%) with maternal uniparental disomy were found, respectively. Of the AS patients, 8 (67%) had a deletion, 1 (8%) paternal uniparental disomy and 3 (25%) biparental inheritance, respectively. Two sibs with biparental disomy showed a typical methylation pattern for AS, indicating that the maternal chromosome 15 carried a paternal methylation imprint. In the DNA methylation analysis the probe PW71 was useful: in our study it detected all deletions and uniparental disomy patients as well as potential imprinting mutations. The probe DN34 couldn`t identify patients which have a deletion outside the D15S9 locus. In the diagnosis of AS and PWS, the differential methylation of the parental 15q11-q13 offers a rapid diagnostic test but does not distinguish between a deletion and uniparental disomy. In our material the probe 4a.1, which detects DNA sequences from both the locus SNRPN (15q12) and SNRPNP1 (6pter-p21), proved to be reliable detecting all deletions. For detection of parental origin of deletion or uniparental disomy, microsatellite markers proved useful.
- OSTI ID:
- 134236
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0972
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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