title: 1031-1034delTAAC (Leu125Stop): a novel familial UBE3A mutation causing Angelman syndrome in two siblings showing distinct phenotypes.
abstract: BACKGROUND
  More than 50 mutations in the UBE3A gene (E6-AP ubiquitin protein ligase gene) have been found in Angelman syndrome patients with no deletion, no uniparental disomy, and no imprinting defect.
  
  
  METHODS
  We here describe a novel UBE3A frameshift mutation in two siblings who have inherited it from their asymptomatic mother. Despite carrying the same UBE3A mutation, the proband shows a more severe phenotype whereas his sister shows a milder phenotype presenting the typical AS features.
  
  
  CONCLUSIONS
  We hypothesized that the mutation Leu125Stop causes both severe and milder phenotypes. Potential mechanisms include: i) maybe the proband has an additional problem (genetic or environmental) besides the UBE3A mutation; ii) since the two siblings have different fathers, the UBE3A mutation is interacting with a different genetic variant in the proband that, by itself, does not cause problems but in combination with the UBE3A mutation causes the severe phenotype; iii) this UBE3A mutation alone can cause either typical AS or the severe clinical picture seen in the proband.
authors.affiliation: Department of Genetics, Medical School of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil. gamolf@fmrp.usp.br
authors.forename: Greice Andreotti
authors.initials: GA
authors.lastname: De Molfetta
authors.forename: Cristiane Ayres
authors.initials: CA
authors.lastname: Ferreira
authors.forename: Daniel Onofre
authors.initials: DO
authors.lastname: Vidal
authors.forename: Liane de Rosso
authors.initials: Lde R
authors.lastname: Giuliani
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Maldonado
authors.forename: Wilson Araujo
authors.initials: WA
authors.lastname: Silva
mesh_terms: D000293:Adolescent; D017204:Angelman Syndrome / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA; D035781:Siblings; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases