1031-1034delTAAC (Leu125Stop): a novel familial <it>UBE3A</it> mutation causing Angelman syndrome in two siblings showing distinct phenotypes

<p>Abstract</p> <p>Background</p> <p>More than 50 mutations in the <it>UBE3A</it> gene (E6-AP ubiquitin protein ligase gene) have been found in Angelman syndrome patients with no deletion, no uniparental disomy, and no imprinting defect.</p> <p>Case Presentation</p> <p>We here describe a novel <it>UBE3A</it> frameshift mutation in two siblings who have inherited it from their asymptomatic mother. Despite carrying the same <it>UBE3A</it> mutation, the proband shows a more severe phenotype whereas his sister shows a milder phenotype presenting the typical AS features.</p> <p>Conclusions</p> <p>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 <it>UBE3A</it> mutation; ii) since the two siblings have different fathers, the <it>UBE3A</it> mutation is interacting with a different genetic variant in the proband that, by itself, does not cause problems but in combination with the <it>UBE3A</it> mutation causes the severe phenotype; iii) this <it>UBE3A</it> mutation alone can cause either typical AS or the severe clinical picture seen in the proband.</p