Mutational analysis of ATP7B in north Chinese patients with Wilson disease

Li, Kui; Zhang, Weimin; Lin, Sheng; Wen, Lu; Wang, Zi-Feng; Xie, Dan; Min, Wei; Qiu, Zhengqing; Dai, Yi; Lin, Marie C.; Kung, Hsiang‐Fu; Yao, Feng

doi:10.1038/jhg.2012.134

Cited by 26 publications

(24 citation statements)

References 41 publications

(56 reference statements)

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“…Eight of the nine novel mutations were missense or non-sense mutations that were classified as Damaging II type or Truncated type, and are thus probably to badly impair the function of the ATP7B-encoded protein. The most prevalent mutant allele in this study was the p.Arg778Leu mutation (31.8%), which was consistent with previous studies that identified the same mutation in about 30% of mutant alleles of East Asian patients (Korean, 37.9%; Japanese, 13.4%; and Taiwanese, between 27% and 43.1%) (25,39,46). The p.Pro992Leu allele, the second most frequent mutation (18.54%), was also consistent with a previous report in Taiwanese WD patients (14.5%), but much higher than the 0.4% frequency found in Korean WD patients (38,47).…”

Section: Discussionsupporting

confidence: 93%

“…To determine the ATP7B genotypes and discover novel ATP7B mutations among our Chinese WD patients, we used a two-stage process of PCR-MassArray and direct-sequencing analyses. The detection rate in the studied 1222 WD patients reached 100%, which was higher than the 70-90% attained in prior studies (22,24,25,37,39,41,45). We identified 88 mutations that may reflect the mutational spectrum of ATP7B in Chinese WD patients.…”

Section: Discussionmentioning

confidence: 53%

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Spectrum of ATP7B mutations and genotype–phenotype correlation in large‐scale Chinese patients with Wilson Disease

Cheng

Wang

et al. 2017

Clinical Genetics

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Wilson disease (WD), an inherited disorder associated with ATP7B gene, has a wide spectrum of genotypes and phenotypes. In this study, we developed a rapid multiplex PCR-MassArray method for detecting 110 mutant alleles of interest, and used it to examine genomic DNA from 1222 patients and 110 healthy controls. In patients not found to have any mutation in the 110 selected alleles, PCR-Sanger sequencing was used to examine the ATP7B gene. We identified 88 mutations, including 9 novel mutations. Our analyses revealed p.Arg778Leu, p.Arg919Gly and p.Thr935Met showed some correlations to phenotype. The p.Arg778Leu was related to younger onset age and lower levels of ceruloplasmin (Cp) and serum copper, while p.Arg919Gly and p.Thr935Met both indicated higher Cp levels. Besides, the p.Arg919Gly was related to neurological subtype, and p.Thr935Met showed significant difference in the percentage of combined neurological and visceral subtype. Moreover, for ATP7B mutations, the more severe impact on ATP7B protein was, the younger onset age and lower Cp level presented. The feasibility of presymptomatic DNA diagnosis and predicting clinical manifestation or severity of WD would be facilitated with identified mutations and genotype-phenotype correlation precisely revealed in the study.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 53%

Spectrum of ATP7B mutations and genotype–phenotype correlation in large‐scale Chinese patients with Wilson Disease

Cheng

Wang

et al. 2017

Clinical Genetics

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“…because of technical and diagnostic limitations, Wd is considered a rare disease and has not received much attention 8,9 . in addition, because it is highly clinically and genetically heterogeneous and has complex clinical manifestations during its early stages, this disease is prone to misdiagnosis and missed diagnosis [10][11][12] . therefore, epidemiological investigations of the prevalence and incidence of Wd in populations are important and may improve the diagnosis and treatment of the disease and avoid misdiagnosis and improper treatment.…”

Section: Discussionmentioning

confidence: 99%

Wilson Disease in the South Chinese Han Population

Cheng¹,

Wang

Hu³

et al. 2014

Can. J. Neurol. Sci.

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Wilson disease (Wd), also known as hepatolenticular degeneration (hld), is an autosomal recessive genetic disorder involving disruption of copper metabolism. Wilson disease is caused by mutations in the ATP7B gene on chromosome 13q14.3 encoding a p-type copper transporting adenosine triphosphate (atp) enzyme. the mutations of ATP7B gene leads to obstacles in bile excretion of copper in the liver and to obstacles in combination of copper with ceruloplasmin. it also causes the emergence of characteristic biochemical changes, including decreased ceruloplasmin (Cp) levels in the serum, increased copper content in the liver, and increased 24-hour urinary copper level. due to excessive deposition of copper in the liver, brain, kidney, cornea, and other tissues and organs, the main clinical ABSTRACT: Purpose: to prospectively investigate the incidence and prevalence of Wilson disease (Wd) in Chinese han population in anhui province, to analyze the genetic mutations in individuals with Wd, and to provide basic epidemiological data regarding Wd in this Chinese han population. Methods: between november 2008 and June 2010, individuals aged from 7 to 75 years were screened for the cornea K-f ring in both eyes using slit lamp examination and random sampling methods based on age stratification and cluster level 1. the participants were from anhui province's hanshan County, Jinzhai County, and lixin County. the clinical manifestations of the brain, liver, kidney, skin, and other organs in each individual were also determined. individuals with positive K-f rings and clinical manifestations indicative of Wd underwent copper biochemistry evaluations, abdominal ultrasound testing, and ATP7B gene mutation screening to confirm or exclude the diagnosis of Wd. Results: of 153,370 individuals investigated in this study, nine were diagnosed with Wd. in these Wd individuals, three cases had neurological symptoms, one has hepatic symptoms, one was hepatic and neurological combined, and the other four cases were presymptomatic. of the eight individuals in whom genetic mutations were detected, seven individuals had mutations in the ATP7B gene. the other individual had no ATP7B gene mutations but her copper biochemical test results met the diagnostic criteria for Wd. the incidence and prevalence of Wd in this population were approximately 1.96/100,000 and 5.87/100,000 respectively. Conclusion: the Chinese han population had a higher average prevalence of Wd than the populations of the united States or europe. Chez ces individus atteints de la MW, trois présentaient des manifestations neurologiques, un présentait des manifestations hépatiques, un présentait des manifestations hépatiques et neurologiques et les quatre autres étaient présymptomatiques. parmi les 8 individus chez qui des mutations génétiques ont été détectées, 7 avaient des mutations du gène atp7b. l'autre individu n'avait pas de mutation du gène atp7b mais ses résultats biochimiques pour le dosage du cuivre rencontraient les critères diagnostiques de la MW. l'incidence et la pr...

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“…These mutations are high frequent spots in the Chinese population (Li et al, 2013;Wu et al, 2001a). It has been reported that patients carrying R778L often have severe clinical symptoms (Wu et al, 2001b(Wu et al, , 2003a, and we found that T935M is associated with late disease onset and mild symptoms (unpublished data).…”

Section: Introductionmentioning

confidence: 97%