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Novel mutations found in the ATP7B gene in Chinese patients with Wilson's disease.

ABSTRACT:

Background

Wilson's disease (WD) is an autosomal recessive genetic disease caused by mutations in ATP7B and characterized by copper metabolism disorders.

Methods

Direct sequencing of the ATP7B gene is the most sensitive and widely used confirmatory testing method. Fourteen probands with WD and 12 family members participated in this study. The ATP7B gene was analyzed by direct sequencing.

Results

Twenty-nine different variants (27 substitutions, 1 duplication, 1 deletion) were found. Of the 23 reported variants, nine nondisease variants, 11 disease variants, one silent variant, and two variants with uncertain functions were identified. The six novel variants included c.1875T>A, c.2306T>C, c.3028A>G, c.3243G>A, c.3437_3438 delTG, and c.3903+5G>A.

Conclusion

These findings will assist in the diagnosis of WD. The novel variants have enriched the WD database.

SUBMITTER: Qian Z

PROVIDER: S-EPMC6503029 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Novel mutations found in the ATP7B gene in Chinese patients with Wilson's disease.

Qian Zhiling Z Cui Xiongwei X Huang Yunli Y Liu Yanmin Y Li Ning N Zheng Sujun S Jiang Jun J Cui Shichang S

Molecular genetics & genomic medicine 20190318 5

<h4>Background</h4>Wilson's disease (WD) is an autosomal recessive genetic disease caused by mutations in ATP7B and characterized by copper metabolism disorders.<h4>Methods</h4>Direct sequencing of the ATP7B gene is the most sensitive and widely used confirmatory testing method. Fourteen probands with WD and 12 family members participated in this study. The ATP7B gene was analyzed by direct sequencing.<h4>Results</h4>Twenty-nine different variants (27 substitutions, 1 duplication, 1 deletion) we ...[more]

PMID: 30884209

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Project description:[This corrects the article DOI: 10.3389/fneur.2023.1231605.].

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Novel mutations in <i>ATP7B</i> in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane.

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Mutational analysis of ATP7B in Chinese Wilson disease patients.

Project description:Wilson Disease (WD) is an inborn error of copper metabolism inherited in an autosomal recessive manner caused by the mutations in the P-type ATPase gene (ATP7B). In this study, we screen and detect the mutations of the ATP7B gene in unrelated Chinese WD patients. A total of 68 individuals from ten provinces of China with WD were recruited. Of them, 43 were males and 25 were females, and their onset ages were from 1 to 48 years with a median onset age of 22.2 years. All the exons and exon/intron boundaries of ATP7B gene of the patients were sequenced and aligned to the referred ATP7B gene sequence. The results suggested that 66 of the 68 patents carried with at least one mutation and 48 different mutations were identified including 34 missense, one synonymous, two nonsense, two splicing, and nine frameshift mutations (five insertion and four deletion). Among these mutations, c.2333G>T, c.2310C>G, c.2975C>T, and c.3443T>C were the most prevalent mutants and c.2310C>G always linked with c.2333G>T. The eighth, 11(th), and 18(th) exons carried more mutations (6/48, 5/48, and 5/48, respectively) than others. After comparing with the mutations reported previously, 22 out of the 48 mutations were identified as novel mutations. A popular algorithm, Polyphen-2, was used to predict the effects of the amino-acid substitution due to the mutations on the structure and function of ATP7B function and the predicted results indicated that all the missense mutations were unfavorable except c.121A>G and c.748G>A. Phenotype/genotype correlation analysis suggested that the patients with c.2975C>T or c.3809A>G often presented WD features before 12 years old while the patients with c.3443T>C almost presented WD after 12 years old. This is the first time to identify the common mutations contributing to early onset age in Chinese WD patients. Our study will broaden our knowledge about ATP7B mutations in WD patients.

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