RT Journal Article
SR Electronic
T1 Linkage analysis with chromosome 15q11-13 markers shows genomic imprinting in familial Angelman syndrome.
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 853
OP 857
DO 10.1136/jmg.29.12.853
VO 29
IS 12
A1 E J Meijers-Heijboer
A1 L A Sandkuijl
A1 H G Brunner
A1 H J Smeets
A1 A J Hoogeboom
A1 W H Deelen
A1 J O van Hemel
A1 M R Nelen
A1 D F Smeets
A1 M F Niermeijer
YR 1992
UL http://jmg.bmj.com/content/29/12/853.abstract
AB Angelman syndrome (AS) and Prader-Willi syndrome (PWS) have become the classical examples of genomic imprinting in man, as completely different phenotypes are generated by the absence of maternal (AS) or paternal (PWS) contributions to the q11-13 region of chromosome 15 as a result of deletion or uniparental disomy. Apparently, most patients are sporadic cases. The genetic mechanism underlying familial AS has remained enigmatic for a long time. Recently, evidence has been emerging suggesting autosomal dominant inheritance of a detectable or undetectable defect in a gene or genes at 15q11-13, subject to genomic imprinting. The present report describes an unusually large pedigree with segregation of AS through maternal inheritance and apparent asymptomatic transmission through several male ancestors. Deletion and paternal disomy at 15q11-13 were excluded. However, the genetic defect is still located in this region, as we obtained a maximum lod score of 5.40 for linkage to the GABA receptor locus GABRB3 and the anonymous DNA marker D15S10, which have been mapped within or adjacent to the AS critical region at 15q11-13. The size of the pedigree allowed calculation of an odds ratio in favour of genomic imprinting of 9.25 x 10(5). This family illustrates the necessity of extensive pedigree analysis when considering recurrence risks for relatives of AS patients, those without detectable deletion or disomy in particular.