title: Atypical Angelman syndrome due to a mosaic imprinting defect: Case reports and review of the literature.
abstract: Angelman syndrome (AS) is characterized by severe intellectual disability, limited, or absent speech and a generally happy demeanor. The four known etiological mechanisms; deletions, uniparental disomy, imprinting defects, and UBE3A mutation all affect expression of the UBE3A gene at 15q11-q13. An atypical phenotype is seen in individuals who are mosaic for a chromosome 15q11-q13 imprinting defect on the maternal allele. These patients present with a milder phenotype, often with hyperphagia and obesity or non-specific intellectual disability. Unlike typical AS syndrome, they can have a vocabulary up to 100 words and speak in sentences. Ataxia and seizures may not be present, and the majority of individuals do not have microcephaly. Here we review the current literature and present three individuals with atypical AS caused by a mosaic imprinting defect to demonstrate why DNA methylation analysis at the SNRPN locus needs to be considered in a broader clinical context. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Hunter Genetics, Newcastle, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Le Fevre
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Beygo
authors.affiliation: Westmead Hospital, Westmead, Australia.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Silveira
authors.affiliation: Hunter Genetics, Newcastle, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kamien
authors.affiliation: Genetic Medicine, Manchester Academic Health Sciences Centre, St. Mary's Hospital, Manchester, United Kingdom.
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
authors.affiliation: Clinical Genetics Services, South West Sydney Local Health District, Liverpool, Australia.
authors.forename: Alison
authors.initials: A
authors.lastname: Colley
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Buiting
authors.affiliation: Hunter Genetics, Newcastle, Australia.|Hunter Genetics, Genetics of Learning Disability (GOLD) Service, Newcastle, Australia.|Grow Up Well Priority Research Centre, The University of Newcastle, Newcastle, Australia.
authors.forename: Tracy
authors.initials: T
authors.lastname: Dudding-Byth
mesh_terms: D000293:Adolescent; D017204:Angelman Syndrome / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D019175:DNA Methylation; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D018392:Genomic Imprinting; D006801:Humans; D015994:Incidence; D008297:Male; D009030:Mosaicism; D010641:Phenotype; D055517:snRNP Core Proteins / Q000235:genetics
chemical_list: D055517:snRNP Core Proteins
keywords: Angelman syndrome; atypical Angelman; hyperphagia; imprinting center defect; mosaic Angelman