Tuan Pham Le Anh, Nguyen Trong Tue, Nga Le Hoang Bich, Tran Dat Quoc, Ho Cam Tu, Tran Thinh Huy, Ta Van Thanh, Bui The Hung, Tran Van Khanh
Center for Gene-Protein Research, and 2Department of Biochemistry, Hanoi Medical University, Hanoi 100000, Vietnam.
J Genet. 2017 Dec;96(6):933-939. doi: 10.1007/s12041-017-0857-9.
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The gene responsible for WD was discovered in 1993 and is located on chromosome 13 at 13q14.3. It encodes a copper-specific transporting P-type ATPase. Early diagnosis can improve treatment outcome and decrease the rate of disability or even mortality.We used Sanger sequencing to identify mutation hot spots in 55 northern Vietnamese with a clinical diagnosis of WD. Mutations were screened and detected by direct DNA sequencing. A total of 26 different ATP7B gene mutations were identified, including seven novel mutations (five nonsense and two missense mutations). The most frequent mutations were p.Ser105Ter (24.55%), p.Arg778Leu (5.45%) and p.Thr850Ile (4.55%). Mutation detection rate in exon 2 was 34.55% and ranked first, followed by exon 8 with 16.36%, and exon 18 with 10.91% each, thus, exons 2, 8 and 18 are the mutation hot spots for northern VietnameseWD patients. These findings were different from previous studies in Asia. Our research established a suitable strategy for ATP7B gene testing in northern Vietnamese WD patients.
威尔逊病（WD）是一种常染色体隐性铜代谢紊乱疾病。导致WD的基因于1993年被发现，位于13号染色体的13q14.3位置。它编码一种铜特异性转运P型ATP酶。早期诊断可改善治疗效果，降低残疾率甚至死亡率。我们使用桑格测序法来确定55名临床诊断为WD的越南北部患者的突变热点。通过直接DNA测序筛选和检测突变。共鉴定出26种不同的ATP7B基因突变，包括7种新突变（5种无义突变和2种错义突变）。最常见的突变是p.Ser105Ter（24.55%）、p.Arg778Leu（5.45%）和p.Thr850Ile（4.55%）。第2外显子的突变检测率为34.55%，排名第一，其次是第8外显子，为16.36%，第18外显子各为10.91%，因此，第2、8和18外显子是越南北部WD患者的突变热点。这些发现与之前在亚洲的研究不同。我们的研究为越南北部WD患者的ATP7B基因检测建立了合适的策略。
