title: Mutation analysis of 73 southern Chinese Wilson's disease patients: identification of 10 novel mutations and its clinical correlation.
abstract: This study was designed to investigate the molecular basis and the correlation between genotype and phenotype in the southern Chinese patients with Wilson's disease (WD). Genotypes of the ATP7B gene in 73 WD patients were examined by denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing. A total of 38 different disease-causing mutations were identified, including 10 novel mutations: missense mutations (p.Gln707Arg, p.Cys1079Phe, p.Gly1149Glu, p.Ser855Tyr, p.Ala874Pro and p.Ser921Arg), nonsense mutation (p.Arg1228Stop), splice-site mutations (2121+3A>T and 3244-2A>G) and frameshift mutation (1875_1876insAATT). We found that a pair of siblings carried the same genotype but different clinical type, and two patients were found to have three mutations. In addition, we compared the clinical data for p.Arg778Leu homozygotes and compound heterozygotes. Our research has enriched the mutation spectrum of the ATP7B gene in the Chinese population and can serve as the basis for genetic counseling and clinical/prenatal diagnosis to prevent WD in China.
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Wang
authors.forename: Ye-Qing
authors.initials: YQ
authors.lastname: Huang
authors.forename: Xuan
authors.initials: X
authors.lastname: Shang
authors.forename: Quan-Xi
authors.initials: QX
authors.lastname: Su
authors.forename: Fu
authors.initials: F
authors.lastname: Xiong
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Yu
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Lin
authors.forename: Zhi-Sheng
authors.initials: ZS
authors.lastname: Wei
authors.forename: Ming-Fan
authors.initials: MF
authors.lastname: Hong
authors.forename: Xiang-Min
authors.initials: XM
authors.lastname: Xu
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases