Mutations and Polymorphisms in the Human Argininosuccinate Synthetase (ASS1) Gene
Mutations and Polymorphisms in the Human Argininosuccinate Synthetase (ASS1) Gene
复制标题
DOI：
10.1002/humu.20847
复制
发表时间：
2009-03-01
期刊：
影响因子：
3.9
通讯作者：
Haeberle, Johannes
中科院分区：
文献类型：
--
作者：
Engel, Katharina;Hoehne, Wolfgang;Haeberle, Johannes
瓜氨酸血症I型是一种常染色体隐性遗传疾病，由尿素循环酶乙酰氨基琥珀酸合成酶（ASS 1）缺乏引起。ASS 1缺乏症表现出各种临床表现，包括严重影响的致命性新生儿高氨血症患者以及仅具有生化表型的无症状个体。这是一份关于染色体9q34.1上的ASS 1基因中迄今为止发现的所有87种突变的综合报告。大部分的突变（n = 27）在这里首次描述。突变分布在外显子3至15中，其中大多数在外显子5、12、13和14中鉴定。外显子15中的突变G390 R是经典表型患者中最常见的单一突变。某些突变与特定的临床病程明显相关，但临床表型无法在所有患者中预测。本更新介绍了一项调查的相关性在ASS 1基因突变和各自的临床过程中所描述的。它还揭示了突变的地理发生率。酶的研究已经在细菌和人类细胞系统中进行。然而，遗传畸变对蛋白质功能和临床表现的影响的预后价值仍然不确定。参见Mutat 30，300-307，2009。(C)2008 Wiley-Liss，Inc.
Citrullinemia type I is an autosomal recessive disorder that is caused by a deficiency of the urea cycle enzyme argininosuccinate synthetase (ASS1). Deficiency of ASS1 shows various clinical manifestations encompassing severely affected patients with fatal neonatal hyperammonemia as well as asymptomatic individuals with only a biochemical phenotype. This is a comprehensive report of all 87 mutations found to date in the ASS1 gene on chromosome 9q34.1. A large proportion of the mutations (n = 27) are described here for the first time. Mutations are distributed throughout exons 3 to 15, most of them being identified in exons 5, 12, 13, and 14. The mutation G390R in exon 15 is the single most common mutation in patients with the classical phenotype. Certain mutations clearly link to specific clinical courses but the clinical phenotype cannot be anticipated in all patients. This update presents a survey of the correlation between mutations in the ASS1 gene and the respective clinical courses as described so far. It also sheds light on the geographic incidence of the mutations. Enzymatic studies have been done in bacterial and human cell systems. However, the prognostic value of genetic aberrations with respect to their effect on protein function and clinical manifestation remains uncertain. Hum Mutat 30, 300-307, 2009. (C) 2008 Wiley-Liss, Inc.