Mutations and polymorphisms in the human ornithine transcarbamylase gene
Mutations and polymorphisms in the human ornithine transcarbamylase gene
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DOI：
10.1002/humu.10035
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发表时间：
2002-01-01
期刊：
影响因子：
3.9
通讯作者：
Lynch, MG
中科院分区：
文献类型：
--
作者：
Tuchman, M;Jaleel, N;Lynch, MG
鸟氨酸转氨酶(OTC)缺乏症是一种X连锁的半显性遗传性疾病，是尿失禁中最常见的遗传缺陷，导致高氨血症。前两次OTC基因突变更新分别发表于1993年和1995年，分别包括36个和30个突变。这一全面的更新包含244个突变的汇编，其中包括13个多态。其中24个突变是首次在这里报告的。引起突变的42%的疾病与急性新生儿高氨血症有关；21%发现于晚发疾病患者，约37%发现于躁狂症杂合子女性，其中大多数被推定为在半合子男性中授予新生儿表型。还包括残留的酶活性和尿素中残留的铵氮掺入，以及对一小部分突变的表达研究结果。OTC基因的大部分突变是“私有”的，并且分布在整个基因中，在编码前导肽的序列(外显子1和外显子2的开头)和外显子7中几乎没有突变。几乎所有共识剪接位点的突变都赋予了新生儿表型。已经发现了13个多态，其中几个对于找不到突变的患者的等位基因追踪很有用。即使对整个阅读框和外显子/内含子边界进行测序，只有大约80%的突变在已证实的OTC缺乏症患者中被检测到。其余的可能发生在内含子或调控结构域中。Hum Mutat 19：93-107,2002。(C)2002年Wiley-Liss，Inc.
Ornithine transcarbamylase (OTC) deficiency, an X-linked, semidominant disorder, is the most common inherited defect in ureagenesis resulting in hyperammonemia. The previous two mutation updates for the OTC gene were published in 1993 and 1995 and included 36 and 30 mutations respectively. This comprehensive update contains a compilation of 244 mutations including 13 polymorphisms. Twenty-four of the mutations are reported here for the first time. Forty-two percent of the disease,causing mutations are associated with acute neonatal hyperammonemia; 21% were found in patients with late onset disease and approximately 37% were found in mania festing heterozygous females, most of which are presumed to confer a neonatal phenotype in hemizygous males. Also included are residual enzyme activities and residual incorporation of ammonium nitrogen into urea and results of expression studies for a small proportion of the mutations. Most mutations in the OTC gene are "private" and are distributed throughout the gene with paucity of mutation in the sequence encoding the leader peptide (exon 1 and beginning of exon 2) and in exon 7. Almost all mutations in consensus splicing sites confer a neonatal phenotype. Thirteen polymorphisms have been found, several of which are useful for allele tracking in patients in whom the mutation cant be found. Even with sequencing of the entire reading frame and exon/intron boundaries, only about 80% of the mutations are detected in patients with proven OTC deficiency. The remaining probably occur within the introns or in regulatory domains. Hum Mutat 19:93-107, 2002. (C) 2002 Wiley-Liss, Inc.