title: Deletion of UBE3A in brothers with Angelman syndrome at the breakpoint with an inversion at 15q11.2.
abstract: 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.
authors.affiliation: Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ohashi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Saito
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Nagai
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ida
authors.forename: Takuya
authors.initials: T
authors.lastname: Naruto
authors.forename: Takahito
authors.initials: T
authors.lastname: Wada
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
mesh_terms: D017204:Angelman Syndrome / Q000175:diagnosis / Q000235:genetics*; 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 / Q000235:genetics*
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases
keywords: 15q inversion; Angelman syndrome; UBE3A deletion; chromosomal rearrangement; familial cases