Identification of novel mutations and the three most common mutations in the human ATP7B gene of Korean patients with Wilson disease

Yoo, Han‐Wook

doi:10.1097/00125817-200211001-00009

Cited by 55 publications

(40 citation statements)

References 13 publications

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“…Several groups have reported WD patients without coding mutations in ATP7B [14,22,23]. The high frequency of normal ATP7B coding alleles in this large WD cohort and other studies suggests that other mechanisms besides coding mutations in ATP7B could account for a significant number of WD cases.…”

Section: Resultssupporting

confidence: 49%

Wilson Disease Mutations in the American Population: Identification of Five Novel Mutations in ATP7B

Kuppala¹,

Deng²,

Brewer³

et al. 2009

TOHEPATJ

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Abstract:Wilson disease is an autosomal recessive disorder characterized by toxic accumulation of copper in a number of organs such as liver and brain, which results in significant disability or death if left untreated. Wilson disease is caused by mutations in ATP7B, a copper transporter. We analyzed 108 American Wilson disease patients, who are predominantly White, for mutations in ATP7B. Consistent with studies from other populations, H1069Q was the most common mutation in this group of patients, accounting for 40.3% of the sequenced alleles; 26 of the 108 patients were homozygous, and 35 patients were heterozygous for this mutation. We also identified 24 additional ATP7B mutations, of which five were novel. The five new mutations consist of two insertion mutations (2302insT and 3843insT), one splice site mutation (IVS11+2:T>A), one combination of deletion (2bp) and insertion (19bp) (3693-3697delins19bp), and one missense mutation (G1213S). All variants are predicted to be disease-causing mutations. Ninety six percent of all mutations we identified were clustered in regions encoding the C-terminal half (catalytic domain) of the ATP7B protein. Furthermore, we found that 84% of the mutant alleles identified in the American population are located in exons 14 and 18.

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Section: Resultssupporting

confidence: 49%

Wilson Disease Mutations in the American Population: Identification of Five Novel Mutations in ATP7B

Kuppala¹,

Deng²,

Brewer³

et al. 2009

TOHEPATJ

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“…The four most common mutations were c.2333G [ T or p.R778L (17.3%), c.2975C [ T or p.P992L (13.4%), c.3443T [ C or p.I1148T (8.7%), and c.3532A [ G or p.T1178A (5.5%). The mutation detection rate achieved was 97.6% (126 disease alleles found in 129 unrelated WD chromosomes) and was the highest among other major Asian studies (Okada et al 2000;Park et al 2007;Wan et al 2006;Wu et al 2001;Yoo 2002). In three patients, we found only one WD mutant allele after sequencing all the ATP7B exons and approximately 1 kb of each 5 0 and 3 0 untranslated region.…”

Section: Resultsmentioning

confidence: 59%

“…Although p.R778L is still the most prevalent mutation in East Asia, our study reported the lowest allele frequency of p.R778L (17.3%) among Hong Kong Han Chinese patients: 2.6-fold lower than Han patients from Northern China (45.6%, v 2 = 27.9, p \ 0.0001) (Liu et al 2004) and significantly lower than patients from Beijing, Fujian, Shandong, Jiangxi, Shanghai, and Zhejiang (37.7%, v 2 = 14.2, p = 0.0002) (Wu et al 2001), from Shandong, Hebei, Anhui, Sichuan, Jiangsu, and Liaoning (33.8%, v 2 = 8.1, p = 0.0043) (Gu et al 2003), from Korea (37.9%, v 2 = 10.8, p = 0.0010) (Yoo 2002), and Taiwan (43.1%, v 2 = 14.9, p = 0.0001) (Wan et al 2006). Despite being two different ethnic populations, Korean and Northern Han Chinese shared almost an identical allele frequency of p.R778L in WD patients.…”

Section: Discussionmentioning

confidence: 95%

“…The rest of the mutations are highly variable. Most mutations lie on exons 8, 12, 13, 16, and 18 in Northern Chinese covering 60.5-74% mutations (Liu et al 2004;Wu et al 2001);exons 8, 12, 13, 16, and 18 in Taiwanese with coverage of 61.8% (Wan et al 2006); exons 8, 11, and 18 in Koreans with coverage of 59.8-71.4% (Park et al 2007;Yoo 2002);and exons 5, 8, 12, 13, and 18 in Japanese with coverage of 60.9-70% (Okada et al 2000;Shimizu et al 1999). We proposed a five-exon screening approach to Hong Kong Han Chinese.…”

Section: Discussionmentioning

confidence: 99%

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Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity

et al. 2007

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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.

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“…The most frequent WND mutations were p.Arg778Leu and p.Pro992Leu, which account for 50.43% of all the reported WND alleles in Chinese population [33,34]. The R778L mutation was also frequent in Korean and Taiwan population with an allele frequency of 20-35% & 55.4% [35,36,37]. In addition to R778L mutation at exon 8, hotspot for ATP7B mutation in exon 12 were also detected in Taiwan WND patients [38] where 9.62% of all mutations occurred.…”

Section: Resultsmentioning

confidence: 99%

PCR in Disease Diagnosis of WND

Majeed¹,

Naveed²,

Rehman³

et al. 2012

Polymerase Chain Reaction

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Identification of novel mutations and the three most common mutations in the human ATP7B gene of Korean patients with Wilson disease

Cited by 55 publications

References 13 publications

Wilson Disease Mutations in the American Population: Identification of Five Novel Mutations in ATP7B

Wilson Disease Mutations in the American Population: Identification of Five Novel Mutations in ATP7B

Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity

PCR in Disease Diagnosis of WND

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