1031-1034delTAAC (Leu125Stop): a novel familial UBE3A mutation causing Angelman syndrome in two siblings showing distinct phenotypes
1 Department of Genetics, Medical School of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
2 Regional Blood Center of Ribeirao Preto and National Institute of Science and Technology in Cell Therapy, Ribeirao Preto, Brazil
3 Department of Pediatrics, Federal University of Mato Grosso do Sul, Campo Grande, Brazil
4 CTC – Centro de Terapia Celular da Fundação Hemocentro de Ribeirão Preto, Laboratório de Genética Molecular e Bioinformática, Depto. De Genética, Rua Tenente Catão Roxo, 2501, 14051-140, Ribeirão Preto, São Paulo, Brazil
BMC Medical Genetics 2012, 13:124 doi:10.1186/1471-2350-13-124Published: 20 December 2012
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.
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.
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.