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Article: Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity
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TitleMutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity
 
AuthorsMak, CM4 6
Lam, CW4
Tam, S6
Lai, CL1
Chan, LY4
Fan, ST1
Lau, YL1
Lai, JY2
Yuen, P4
Hui, J4
Fu, CC4
Wong, KS4
Mak, WL3
Tze, K3
Tong, SF4
Lau, A4
Leung, N7
Hui, A7
Cheung, KM8
Ko, CH8
Chan, YK8
Ma, O6
Chau, TN5
Chiu, A6
Chan, YW2
 
KeywordsATP7B
Genotype
Haplotype
Hong Kong Chinese
Novel mutation
P.R778L founder mutation
Wilson disease
 
Issue Date2008
 
PublisherSpringer Japan. The Journal's web site is located at http://link.springer.de/link/service/journals/10038/index.htm
 
CitationJournal Of Human Genetics, 2008, v. 53 n. 1, p. 55-63 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s10038-007-0218-2
 
AbstractWilson 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. © 2007 The Japan Society of Human Genetics and Springer.
 
ISSN1434-5161
2012 Impact Factor: 2.365
2012 SCImago Journal Rankings: 0.935
 
DOIhttp://dx.doi.org/10.1007/s10038-007-0218-2
 
ISI Accession Number IDWOS:000251827900007
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorMak, CM
 
dc.contributor.authorLam, CW
 
dc.contributor.authorTam, S
 
dc.contributor.authorLai, CL
 
dc.contributor.authorChan, LY
 
dc.contributor.authorFan, ST
 
dc.contributor.authorLau, YL
 
dc.contributor.authorLai, JY
 
dc.contributor.authorYuen, P
 
dc.contributor.authorHui, J
 
dc.contributor.authorFu, CC
 
dc.contributor.authorWong, KS
 
dc.contributor.authorMak, WL
 
dc.contributor.authorTze, K
 
dc.contributor.authorTong, SF
 
dc.contributor.authorLau, A
 
dc.contributor.authorLeung, N
 
dc.contributor.authorHui, A
 
dc.contributor.authorCheung, KM
 
dc.contributor.authorKo, CH
 
dc.contributor.authorChan, YK
 
dc.contributor.authorMa, O
 
dc.contributor.authorChau, TN
 
dc.contributor.authorChiu, A
 
dc.contributor.authorChan, YW
 
dc.date.accessioned2010-09-06T07:33:24Z
 
dc.date.available2010-09-06T07:33:24Z
 
dc.date.issued2008
 
dc.description.abstractWilson 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. © 2007 The Japan Society of Human Genetics and Springer.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Human Genetics, 2008, v. 53 n. 1, p. 55-63 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s10038-007-0218-2
 
dc.identifier.doihttp://dx.doi.org/10.1007/s10038-007-0218-2
 
dc.identifier.epage63
 
dc.identifier.hkuros141602
 
dc.identifier.isiWOS:000251827900007
 
dc.identifier.issn1434-5161
2012 Impact Factor: 2.365
2012 SCImago Journal Rankings: 0.935
 
dc.identifier.issue1
 
dc.identifier.openurl
 
dc.identifier.pmid18034201
 
dc.identifier.scopuseid_2-s2.0-37549012199
 
dc.identifier.spage55
 
dc.identifier.urihttp://hdl.handle.net/10722/77576
 
dc.identifier.volume53
 
dc.languageeng
 
dc.publisherSpringer Japan. The Journal's web site is located at http://link.springer.de/link/service/journals/10038/index.htm
 
dc.publisher.placeJapan
 
dc.relation.ispartofJournal of Human Genetics
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAsian Continental Ancestry Group
 
dc.subject.meshDNA Mutational Analysis
 
dc.subject.meshGene Frequency
 
dc.subject.meshGenetic Heterogeneity
 
dc.subject.meshHaplotypes
 
dc.subject.meshHepatolenticular Degeneration - genetics
 
dc.subject.meshHong Kong
 
dc.subject.meshHumans
 
dc.subject.meshLinkage Disequilibrium
 
dc.subject.meshMutation
 
dc.subjectATP7B
 
dc.subjectGenotype
 
dc.subjectHaplotype
 
dc.subjectHong Kong Chinese
 
dc.subjectNovel mutation
 
dc.subjectP.R778L founder mutation
 
dc.subjectWilson disease
 
dc.titleMutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Princess Margaret Hospital Hong Kong
  3. Tuen Mun Hospital
  4. Prince of Wales Hospital Hong Kong
  5. United Christian Hospital Hong Kong
  6. Queen Mary Hospital Hong Kong
  7. Alice Ho Miu Ling Nethersole Hospital
  8. Caritas Medical Centre Hong Kong