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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 5,500 years.
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            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 5,500 years.
      datePublished:2008-01-01T00:00:00Z
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          ATP7B
         p.R778L founder mutation
         Genotype
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         Novel mutation
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         Human Genetics
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      address:
         name:Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
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         name:Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
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         name:Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
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         name:Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
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         name:Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
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      address:
         name:Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China
         type:PostalAddress
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         name:Department of Pediatrics and Adolescent Medicine, Caritas Medical Center, Hong Kong, China
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         name:Department of Pediatrics and Adolescent Medicine, Caritas Medical Center, Hong Kong, China
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      address:
         name:Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, China
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         name:Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong, China
         type:PostalAddress
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      address:
         name:Department of Adult Intensive Care Unit, Queen Mary Hospital, Hong Kong, China
         type:PostalAddress
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      address:
         name:Department of Pathology, Princess Margaret Hospital, Hong Kong, China
         type:PostalAddress
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      name:Chloe Miu Mak
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            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
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            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
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            address:
               name:Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, China
               type:PostalAddress
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            name:The University of Hong Kong, Queen Mary Hospital
            address:
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            address:
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            address:
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            name:The Chinese University of Hong Kong, Prince of Wales Hospital
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      affiliation:
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            address:
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      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
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      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
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      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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