Angelman and Prader‐Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion

Abstract

Many Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients have a cytogenetic deletion of 15q11q13. While AS and PWS share a similar cytogenetic anomaly, they have very different clinical phenotypes. DNAs from 4 AS patients were examined using 5 chromosome 15q11q13-specific cloned DNA segments. With the present level of resolution, the molecular deletions between AS and those previously reported for PWS did not appear to differ. However, in contrast to the paternal inheritance of the deleted chromosome 15 observed in the majority of PWS patients, maternal inheritance of the deleted chromosome 15 was demonstrated in the AS patients by restriction fragment length polymorphisms (RFLPs).

The behavioural phenotype of Angelman syndrome

“…It was initially proposed that Angelman and Prader-Willi syndromes resulted from deletions of different points along the long arm of chromosome 15 (Magenis et al, 1987). In 1989, however it was observed that the deletion of 15q11-13, which resulted in Angelman syndrome, was on the chromosome 15 that had been inherited from the mother and in Prader-Willi syndrome the deletion was derived from the father (Knoll, Nicholls, Magenis, Graham, Lalande & Latt, 1989). These two syndromes then provided a human model for genomic imprinting, where genetic information is expressed differently depending on the parent of origin (Clayton-Smith, 1992).…”

Angelman syndrome: a review of clinical and genetic aspects

“…26 Most deletions occur de novo and are of maternal origin, in contrast to the 15q11-13 deletions observed in Prader-Willi syndrome which are of paternal origin. 27 The common deletion can be detected by FISH analysis and by methylation analysis of the SNRPN (small nuclear ribonucleoprotein polypeptide N) promoter which lies within a CpG island at 15q11-13. In the presence of a maternal deletion only the paternal, unmethylated pattern will be detectable.…”

Detection of Imprinted Genes by Single-Cell Allele-Specific Gene Expression

“…For instance, some imprinted genes play a decisive role in growth control and developmental processes. 6 The disruption of these genes causes severe genetic syndromes including Prader-Willi syndrome (PWS [MIM: 176270]), Angelman syndrome (AS [MIM: 105830]), [7][8][9] Beckwith-Wiedemann syndrome (BWS [MIM: 130650]), [10][11][12] Silver-Russell syndrome (SRS [MIM: 180860]), 13,14 Temple syndrome (TS14 [MIM: 616222]), and Kagami-Ogata syndrome (KOS14 [MIM: 608149]). 15 In the early 1990s, Igf2 (paternally expressed) and H19 (maternally expressed) were the first two imprinted genes to be discovered in mice.…”