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

BMC Medical Genetics

Wilson Araujo Silva²  Maria José Maldonado¹  Liane de Rosso Giuliani¹  Daniel Onofre Vidal³  Cristiane Ayres Ferreira³  Greice Andreotti De Molfetta² 

[1] Department of Pediatrics, Federal University of Mato Grosso do Sul, Campo Grande, Brazil;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;Regional Blood Center of Ribeirao Preto and National Institute of Science and Technology in Cell Therapy, Ribeirao Preto, Brazil

关键词: HRM;    Distinct phenotypes;    Novel mutation;    Imprinting;    UBE3A gene;    Angelman syndrome;   

Others  :  1177755
DOI  :  10.1186/1471-2350-13-124

 received in 2011-12-19, accepted in 2012-12-13,  发布年份 2012

【 摘 要 】

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.

Case Presentation

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.

【 授权许可】

   
2012 De Molfetta et al.; licensee BioMed Central Ltd.

【 图 表 】

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