Deletion of UBE3A in brothers with Angelman syndrome at the breakpoint with an inversion at 15q11.2.
Angelman syndrome (AS) is characterized by severe intellectual disability with ataxia, epilepsy, and behavioral uniqueness. The underlining molecular deficit is the absence of the maternal copy of the imprinted UBE3A gene due to maternal deletions, which is observed in 70-75% of cases, and can be detected using fluorescent in situ hybridization (FISH) of the UBE3A region. Only a few familial AS cases have been reported with a complete deletion of UBE3A. Here, we report on siblings with AS caused by a microdeletion of 15q11.2-q12 encompassing UBE3A at the breakpoint of an inversion at 15q11.2 and 15q26.1. Karyotyping revealed an inversion of 15q, and FISH revealed the deletion of the UBE3A region. Array comparative genomic hybridization (CGH) demonstrated a 467 kb deletion at 15q11.2-q12, encompassing only UBE3A, SNORD115, and PAR1, and a 53 kb deletion at 15q26.1, encompassing a part of SLCO3A1. Their mother had a normal karyotype and array CGH detected no deletion of 15q11.2-q12, so we assumed gonadal mosaicism. This report describes a rare type of familial AS detected using the D15S10 FISH test.
['Kuroda|Yukiko|Y|', 'Ohashi|Ikuko|I|', 'Saito|Toshiyuki|T|', 'Nagai|Jun-Ichi|J|', 'Ida|Kazumi|K|', 'Naruto|Takuya|T|', 'Wada|Takahito|T|', 'Kurosawa|Kenji|K|']
D017204:Angelman Syndrome D002648:Child D002675:Child, Preschool D056905:Chromosome Breakpoints D007446:Chromosome Inversion D002874:Chromosome Mapping D002884:Chromosomes, Human, Pair 15 D055028:Comparative Genomic Hybridization D019066:Facies D017353:Gene Deletion D006801:Humans D017404:In Situ Hybridization, Fluorescence D008297:Male D010641:Phenotype D020641:Polymorphism, Single Nucleotide D035781:Siblings D044767:Ubiquitin-Protein Ligases
Angelman syndrome 15q inversion UBE3A deletion chromosomal rearrangement familial cases