title: Mutational analysis of ATP7B in north Chinese patients with Wilson disease.
abstract: Wilson disease (WD) is an autosomal recessive inherited disease caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in 114 individuals of Chinese Han population living in north China who were diagnosed as WD. Totally, we identified 36 mutations and 11 single-nucleotide polymorphisms (SNPs), of which 14 mutations have never been reported previously and 5 were firstly described in Chinese. Among these, p.R778L (21.5%), p.A874V (7.5%) and p.P992L (6.1%) were the most frequent mutations. A genotype of p.L770L+p.R778L+p.P992L was the most frequent triple mutations and two pairs of mutations, p.L770L/p.R778L and p.A874V/p.I929V, were closely related. In addition, a database was established to summarize all ATP7B mutations, including those reported previously and those identified in this study. Popular algorithms were used to predict the functional effects of these mutations, and finally, by comparative genomics approaches, we predicted a group of mutation hot spots for ATP7B. Our study will broaden our knowledge about ATP7B mutations in WD patients in north China, and be helpful for clinical genetic testing.
authors.affiliation: Laboratory of Integrated Biosciences, Life Science School, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Li
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Zhang
authors.forename: Sheng
authors.initials: S
authors.lastname: Lin
authors.forename: Lu
authors.initials: L
authors.lastname: Wen
authors.forename: Zi-Feng
authors.initials: ZF
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Zheng-Qing
authors.initials: ZQ
authors.lastname: Qiu
authors.forename: Yi
authors.initials: Y
authors.lastname: Dai
authors.forename: Marie C M
authors.initials: MC
authors.lastname: Lin
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Feng-Xia
authors.initials: FX
authors.lastname: Yao
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D002681:China; D000073840:Copper-Transporting ATPases; D005006:Ethnicity / Q000235:genetics; D005260:Female; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases