三磷酸腺苷酶缺乏综合征的基因异质性与临床表型：国立卫生研究院2000 - 2005年经验综述

Genotypic heterogeneity and clinical phenotype in triple A syndrome: a review of the NIH experience 2000-2005.

作者信息

Brooks B P, Kleta R, Stuart C, Tuchman M, Jeong A, Stergiopoulos S G, Bei T, Bjornson B, Russell L, Chanoine J-P, Tsagarakis S, Kalsner Lr, Stratakis Ca

机构信息

Office of the Scientific Director, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

出版信息

Clin Genet. 2005 Sep;68(3):215-21. doi: 10.1111/j.1399-0004.2005.00482.x.

DOI:10.1111/j.1399-0004.2005.00482.x

PMID:16098009

Abstract

Triple A syndrome (AAAS, OMIM#231550) is an autosomal recessive condition characterized by adrenal insufficiency, achalasia, alacrima, neurodegeneration and autonomic dysfunction. Mutations in the AAAS gene on chromosome 12q13 have been reported in several subjects with AAAS. Over the last 5 years, we have evaluated six subjects with the clinical diagnosis of AAAS. Three subjects had mutations in the AAAS gene-- including one novel mutation (IVS8+1 G>A)-- and a broad spectrum of clinical presentations. However, three subjects with classic AAAS did not have mutations in the AAAS gene on both alleles. This finding supports the notion of genetic heterogeneity for this disorder, although other genetic mechanisms cannot be excluded.

摘要

三A综合征（AAAS，OMIM编号#231550）是一种常染色体隐性疾病，其特征为肾上腺功能不全、贲门失弛缓症、无泪、神经退行性变和自主神经功能障碍。12号染色体q13上AAAS基因的突变已在数名三A综合征患者中被报道。在过去5年里，我们评估了6例临床诊断为三A综合征的患者。3例患者的AAAS基因存在突变，包括1个新突变（IVS8+1 G>A），且临床表现多样。然而，3例典型三A综合征患者的两个等位基因上的AAAS基因均未发生突变。这一发现支持了该疾病存在遗传异质性的观点，尽管不能排除其他遗传机制。