title: Mild Angelman syndrome phenotype due to a mosaic methylation imprinting defect.
abstract: Angelman syndrome (AS) is a neurogenetic disorder causing severe to profound intellectual disability, absent or very limited speech and a high risk for seizures. AS is caused by a loss of function of the maternally-derived UBE3A allele due to one of several mechanisms including imprinting defects (ImpDs). We present a girl with AS due to a mosaic ImpD who has relatively high developmental function (VABS-II composite score of 76) and communication skills (as demonstrated in supplemental video links). Given the patient's relatively mild developmental impairment, without clinical evidence of seizures, gait disturbance or inappropriate laughter, the diagnosis of AS was not initially suspected. Initial laboratory testing for AS was inconclusive but additional studies suggested mosaic ImpD and characteristic EEG findings provided further support for the clinical diagnosis. Our patient, along with other case reports of children with AS and relatively mild phenotypes, raises the question as to whether there exists an undiagnosed group of individuals with mild intellectual disability and expressive speech delays due to mosaic methylation defects of the chromosome 15q11.2-13 region. Population studies may be needed to determine if such an undiagnosed group exists.
authors.affiliation: Division of Genetics and Metabolism, Department of Pediatrics, University of Florida, Raymond C. Philips Unit, Gainesville, Florida.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Fairbrother
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics and Genetics and Genome Biology, Research Institute, Hospital for Sick Children, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Ontario, Canada.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cytrynbaum
authors.affiliation: Parent, Toronta, Canada.
authors.forename: Paula
authors.initials: P
authors.lastname: Boutis
authors.affiliation: Institut f, ü, r Humangenetik, Universit, ä, tsklinikum Essen, Essen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Buiting
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics and Genetics and Genome Biology, Research Institute, Hospital for Sick Children, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Ontario, Canada.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
authors.affiliation: Division of Genetics and Metabolism, Department of Pediatrics, University of Florida, Raymond C. Philips Unit, Gainesville, Florida.
authors.forename: Charles
authors.initials: C
authors.lastname: Williams
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics* / Q000473:pathology*; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004569:Electroencephalography; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases
keywords: DNA methylation; MS-MLPA; angelman syndrome; imprinting; imprinting defect; mosaic