A previously unrecognised phenotype characterised by obesity, muscular hypotonia, and ability to speak in patients with Angelman syndrome caused by an imprinting defect.
The clinical features of Angelman syndrome (AS) comprise severe mental retardation, postnatal microcephaly, macrostomia and prognathia, absence of speech, ataxia, and a happy disposition. We report on seven patients who lack most of these features, but presented with obesity, muscular hypotonia and mild mental retardation. Based on the latter findings, the patients were initially suspected of having Prader-Willi syndrome. DNA methylation analysis of SNRPN and D15S63, however, revealed an AS pattern, ie the maternal band was faint or absent. Cytogenetic studies and microsatellite analysis demonstrated apparently normal chromosomes 15 of biparental inheritance. We conclude that these patients have an imprinting defect and a previously unrecognised form of AS. The mild phenotype may be explained by an incomplete imprinting defect or by cellular mosaicism.
Gillessen-Kaesbach
G
G
Institut für Humangenetik, Universitätsklinikum Essen, Germany. g.gillessen@uni-essen.de
Demuth
S
S
Thiele
H
H
Theile
U
U
Lich
C
C
Horsthemke
B
B
D017204:Angelman Syndrome / Q000235:genetics*; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15; D019175:DNA Methylation; D003937:Diagnosis, Differential; D005260:Female; D005819:Genetic Markers; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D009030:Mosaicism; D009123:Muscle Hypotonia / Q000235:genetics*; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction
D005819:Genetic Markers