Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease
Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease
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DOI：
10.1046/j.1399-0004.2003.00179.x
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发表时间：
2003-12-01
影响因子：
3.5
通讯作者：
Ushijima, H
中科院分区：
文献类型：
--
作者：
Gu, YH;Kodama, H;Ushijima, H
肝豆状核变性（WD）是一种常染色体隐性遗传的铜转运障碍，通常表现为累及肝脏或中枢神经系统的症状。该疾病由包含21个表达外显子的ATP 7 B基因中的大量突变引起。一些突变似乎是人群特异性的，而另一些则发现于来自各种不同种族背景的先证者。本文报道了用直接测序法对39例汉族和1例回族患者的ATP 7 B基因进行筛查的结果。沿着发现了19个新的突变，其中有9个先前已经描述过; 57.5%的突变位于外显子8、13和12。特别是，在这些中国患者中，55%的人在至少一个等位基因中发现了外显子8的Arg 778 Leu突变。Arg 778 Leu纯合子5例，杂合子17例。对40例无亲缘关系的患者的ATP 7 B基因所有外显子的PCR产物直接测序，等位基因检出率为83.8%。在患者和健康对照中也发现了17个多态性。我们首次报道了中国回族患者中存在ATP 7 B突变，并将我们的结果与先前报道的结果一起沿着总结于此。Arg 778 Leu纯合子37例，杂合子52例，基因型与表型无显著相关性。
Wilson's disease (WD), an autosomal recessive copper transport disorder, usually presents with symptoms involving the liver or central nervous system. The disease is caused by a large number of mutations in the ATP7B gene comprising 21 expressed exons. Some of the mutations appear to be population specific, whereas others are found in probands from a variety of different ethnic backgrounds. This paper presents the results of screening of the ATP7B gene by means of the direct sequencing of all exons in the gene in 39 Han and one Hui ethnic Chinese patients. Nineteen novel mutations were revealed along with nine others that have been previously described; 57.5% of the mutations were located in exons 8, 13, and 12. In particular, the Arg778Leu mutation in exon 8 was found in 55% of these Chinese patients in at least one allele. Five patients were homozygotes and 17 patients were heterozygotes for Arg778Leu. The detection rate on direct sequencing of the polymerase chain reaction products of all exons of the ATP7B gene in 40 unrelated patients was 83.8% of alleles. Seventeen polymorphisms were also identified in patients and healthy controls. We first reported the presence of ATP7B mutations in Chinese Hui ethnic patients and summarize our results here along with the previously reported findings. A significant correlation between genotype and phenotype was not found in 37 homozygotes and 52 heterozygotes for Arg778Leu.