Panichareon Benjaporn, Taweechue Krailerk, Thongnoppakhun Wanna, Aksornworanart Monthikan, Pithukpakorn Manop, Yenchitsomanus Pa-Thai, Limwongse Chanin, Limjindaporn Thawornchai
Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Eur J Med Genet. 2011 Mar-Apr;54(2):103-7. doi: 10.1016/j.ejmg.2010.10.008. Epub 2010 Oct 27.
WD is an autosomal recessive disorder of copper transport resulting in excessive copper deposition in the liver and brain. It is caused by defects of ATP7B encoding a copper transporting P-type ATPase. To identify the mutations in ATP7B in Thai patients with WD, DHPLC analysis was applied to detect mutations and polymorphisms of the entire ATP7B gene in 19 Thai patients with WD. Mutations in ATP7B were identified in 14 of 19 patients: 2 homozygotes, 8 compound heterozygotes and 4 heterozygotes. Eighteen mutations distributed throughout the entire coding region of ATP7B gene including 11 missense, 3 nonsense, 1 splice-site, 1 deletion and 2 insertions. Of 18 different mutations identified, 6 were found to be novel. Twelve single nucleotide polymorphisms (SNPs) were also identified and two SNPs have not yet previously been reported. Segregation analysis using DHPLC analysis showed mutation transmission patterns within each family of Thai patients with WD. Mutations in ATP7B in Thai patients with WD are worth adding into the public database for genetic epidemiology and population genetics.
威尔逊病是一种常染色体隐性铜转运障碍疾病，会导致肝脏和大脑中铜过度沉积。它由编码铜转运P型ATP酶的ATP7B缺陷引起。为了鉴定泰国威尔逊病患者的ATP7B突变，应用变性高效液相色谱（DHPLC）分析来检测19例泰国威尔逊病患者整个ATP7B基因的突变和多态性。在19例患者中的14例中鉴定出ATP7B突变：2例纯合子、8例复合杂合子和4例杂合子。18种突变分布在ATP7B基因的整个编码区域，包括11种错义突变、3种无义突变、1种剪接位点突变、1种缺失突变和2种插入突变。在鉴定出的18种不同突变中，6种被发现是新的。还鉴定出12个单核苷酸多态性（SNP），其中2个SNP此前尚未见报道。使用DHPLC分析进行的分离分析显示了泰国威尔逊病患者每个家族中的突变传递模式。泰国威尔逊病患者的ATP7B突变值得添加到遗传流行病学和群体遗传学的公共数据库中。
