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Title:
Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity | Journal of Human Genetics
Description:
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.
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headline:Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity
description: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 5,500Â years.
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Human Genetics
Molecular Medicine
Gene Function
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headline:Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity
description: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 5,500Â years.
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p.R778L founder mutation
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Wilson disease
Human Genetics
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Gene Function
Gene Expression
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name:The University of Hong Kong, Queen Mary Hospital
address:
name:Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Lik-Yuen Chan
affiliation:
name:The Chinese University of Hong Kong, Prince of Wales Hospital
address:
name:Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Sheung-Tat Fan
affiliation:
name:The University of Hong Kong, Queen Mary Hospital
address:
name:Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Yu-Lung Lau
affiliation:
name:The University of Hong Kong, Queen Mary Hospital
address:
name:Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Jak-Yiu Lai
affiliation:
name:Princess Margaret Hospital
address:
name:Department of Medicine, Princess Margaret Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Patrick Yuen
affiliation:
name:The Chinese University of Hong Kong, Prince of Wales Hospital
address:
name:Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Joannie Hui
affiliation:
name:The Chinese University of Hong Kong, Prince of Wales Hospital
address:
name:Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Chun-Cheung Fu
affiliation:
name:The Chinese University of Hong Kong, Prince of Wales Hospital
address:
name:Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Ka-Sing Wong
affiliation:
name:The Chinese University of Hong Kong, Prince of Wales Hospital
address:
name:Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Wing-Lai Mak
affiliation:
name:Tuen Mun Hospital
address:
name:Department of Pathology, Tuen Mun Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Kong Tze
affiliation:
name:Tuen Mun Hospital
address:
name:Department of Pediatrics, Tuen Mun Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Sui-Fan Tong
affiliation:
name:The Chinese University of Hong Kong, Prince of Wales Hospital
address:
name:Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Abby Lau
affiliation:
name:The Chinese University of Hong Kong, Prince of Wales Hospital
address:
name:Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Nancy Leung
affiliation:
name:Alice Ho Miu Ling Nethersole Hospital
address:
name:Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Aric Hui
affiliation:
name:Alice Ho Miu Ling Nethersole Hospital
address:
name:Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Ka-Ming Cheung
affiliation:
name:Caritas Medical Center
address:
name:Department of Pediatrics and Adolescent Medicine, Caritas Medical Center, Hong Kong, China
type:PostalAddress
type:Organization
name:Chun-Hung Ko
affiliation:
name:Caritas Medical Center
address:
name:Department of Pediatrics and Adolescent Medicine, Caritas Medical Center, Hong Kong, China
type:PostalAddress
type:Organization
name:Yiu-Ki Chan
affiliation:
name:Caritas Medical Centre
address:
name:Department of Medicine and Geriatrics, Caritas Medical Centre, Hong Kong, China
type:PostalAddress
type:Organization
name:Oliver Ma
affiliation:
name:Queen Mary Hospital
address:
name:Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Tai-Nin Chau
affiliation:
name:United Christian Hospital
address:
name:Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Alexander Chiu
affiliation:
name:Queen Mary Hospital
address:
name:Department of Adult Intensive Care Unit, Queen Mary Hospital, Hong Kong, China
type:PostalAddress
type:Organization
name:Yan-Wo Chan
affiliation:
name:Princess Margaret Hospital
address:
name:Department of Pathology, Princess Margaret Hospital, Hong Kong, China
type:PostalAddress
type:Organization
PostalAddress:
name:Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
name:Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, China
name:Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
name:Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, China
name:Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
name:Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
name:Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
name:Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
name:Department of Medicine, Princess Margaret Hospital, Hong Kong, China
name:Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
name:Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
name:Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
name:Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
name:Department of Pathology, Tuen Mun Hospital, Hong Kong, China
name:Department of Pediatrics, Tuen Mun Hospital, Hong Kong, China
name:Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
name:Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
name:Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China
name:Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China
name:Department of Pediatrics and Adolescent Medicine, Caritas Medical Center, Hong Kong, China
name:Department of Pediatrics and Adolescent Medicine, Caritas Medical Center, Hong Kong, China
name:Department of Medicine and Geriatrics, Caritas Medical Centre, Hong Kong, China
name:Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, China
name:Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong, China
name:Department of Adult Intensive Care Unit, Queen Mary Hospital, Hong Kong, China
name:Department of Pathology, Princess Margaret Hospital, Hong Kong, China
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