Department of Genetics, Medical School of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil.
BMC Med Genet. 2012 Dec 20;13:124. doi: 10.1186/1471-2350-13-124.
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.
在无缺失、单亲二体性和印迹缺陷的 Angelman 综合征患者中，已发现 UBE3A 基因（E6-AP 泛素蛋白连接酶基因）有 50 多种突变。
我们在此描述了一对同患 Angelman 综合征的同胞兄妹，他们从无症状的母亲那里遗传了该基因突变。尽管携带相同的 UBE3A 突变，但先证者表现出更严重的表型，而他的妹妹则表现出较轻的表型，具有典型的 Angelman 综合征特征。
我们假设 Leu125Stop 突变导致了严重和较轻的表型。潜在的机制包括：i）除了 UBE3A 突变之外，先证者可能还有其他问题（遗传或环境）；ii）由于这对同胞兄妹有不同的父亲，UBE3A 突变与先证者中的另一个遗传变异相互作用，该变异本身不会导致问题，但与 UBE3A 突变结合会导致严重表型；iii）该 UBE3A 突变本身可能导致典型的 Angelman 综合征或先证者所见的严重临床表现。
