title: Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: identification of 17 novel mutations and its genetic heterogeneity.
abstract: Wilson disease (WD), an autosomal recessive disorder of copper transport, is the most common inherited liver disorder in Hong Kong Chinese. This was the first local study to elucidate the molecular basis and establish an effective DNA-based diagnostic protocol. The ATP7B genes of 65 patients were amplified by polymerase chain reaction (PCR) and sequenced. Haplotype analysis was performed using D13S301, D13S314, and D13S316. The p.L770L/p.R778L status in 660 subjects was determined to estimate WD prevalence. Allele age of p.R778L was determined by the smallest homozygosity region between D13S301 and D13S270. We identified 42 different mutations with 17 being novel. p.R778L (17.3%) was the most prevalent. Exons 2, 8, 12, 13, and 16 harbored 70% mutations. Thirty-two haplotypes were associated with WD chromosomes. The estimated prevalence rate was 1 in 5,400. Three out of 660 normal subjects had p.L770L/p.R778L. In the remaining 657 individuals, neither p.L770L nor p.R778L was found. We characterized a Hong Kong Chinese-specific ATP7B mutation spectrum with great genetic diversity. Exons 2, 8, 12, 13, and 16 should be screened first. The perfect linkage disequilibrium suggested that p.R778L and its private polymorphism p.L770L originated from a single ancestor. This East-Asian-specific mutation p.R778L/p.L770L is aged at least 5,500 years.
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.|Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, China.
authors.forename: Chloe Miu
authors.initials: CM
authors.lastname: Mak
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China. ching-wanlam@cuhk.edu.hk.
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
authors.affiliation: Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, China.
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Lik-Yuen
authors.initials: LY
authors.lastname: Chan
authors.affiliation: Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors.forename: Sheung-Tat
authors.initials: ST
authors.lastname: Fan
authors.affiliation: Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: Department of Medicine, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Jak-Yiu
authors.initials: JY
authors.lastname: Lai
authors.affiliation: Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Patrick
authors.initials: P
authors.lastname: Yuen
authors.affiliation: Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Joannie
authors.initials: J
authors.lastname: Hui
authors.affiliation: Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Chun-Cheung
authors.initials: CC
authors.lastname: Fu
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Ka-Sing
authors.initials: KS
authors.lastname: Wong
authors.affiliation: Department of Pathology, Tuen Mun Hospital, Hong Kong, China.
authors.forename: Wing-Lai
authors.initials: WL
authors.lastname: Mak
authors.affiliation: Department of Pediatrics, Tuen Mun Hospital, Hong Kong, China.
authors.forename: Kong
authors.initials: K
authors.lastname: Tze
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
authors.forename: Sui-Fan
authors.initials: SF
authors.lastname: Tong
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
authors.forename: Abby
authors.initials: A
authors.lastname: Lau
authors.affiliation: Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China.
authors.forename: Nancy
authors.initials: N
authors.lastname: Leung
authors.affiliation: Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China.
authors.forename: Aric
authors.initials: A
authors.lastname: Hui
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Caritas Medical Center, Hong Kong, China.
authors.forename: Ka-Ming
authors.initials: KM
authors.lastname: Cheung
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Caritas Medical Center, Hong Kong, China.
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Ko
authors.affiliation: Department of Medicine and Geriatrics, Caritas Medical Centre, Sham Shui Po, Hong Kong, China.
authors.forename: Yiu-Ki
authors.initials: YK
authors.lastname: Chan
authors.affiliation: Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, China.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ma
authors.affiliation: Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong, China.
authors.forename: Tai-Nin
authors.initials: TN
authors.lastname: Chau
authors.affiliation: Department of Adult Intensive Care Unit, Queen Mary Hospital, Hong Kong, China.
authors.forename: Alexander
authors.initials: A
authors.lastname: Chiu
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Yan-Wo
authors.initials: YW
authors.lastname: Chan
mesh_terms: D044466:Asian People; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D006239:Haplotypes; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006723:Hong Kong; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation