Identification of two novel mutations in the ATP7B gene that cause Wilson’s disease

Zhu, Hongwen; Tao, Zhongbin; Su, Gang; Jin, Qiao-Ying; Zhao, Liangtao; Zhu, Jinxia; Yan, Jun X.; Yu, Tianyu; Ding, Jie-xian; Li, Yumin

doi:10.1007/s12519-017-0055-0

Cited by 2 publications

(2 citation statements)

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“…Screening patients from the 14 eligible reports [14][15][16][17][18][19][20][21][22][23][24][25][26][27] identified 108 patients with clear WD features. We We observed that the patients with mixed manifestation were significantly older at symptom onset than patients with hepatic symptoms (24.4 V 19.4 years of age, P = 0.039) and patients with neurological symptoms (24.4 V 17.9 years of age, P = 0.015).…”

Section: Characterisation Of Clinical Phenotypementioning

confidence: 99%

Mutation analysis of the ATP7B gene and genotype–phenotype correlation in Chinese patients with Wilson disease

Wen-long

et al. 2021

BMC Gastroenterol

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Aim To discover the novel ATP7B mutations in 103 southern Chinese patients with Wilson disease (WD), and to determine the spectrum and frequency of mutations in the ATP7B gene and genotype–phenotype correlation in a large-scale sample of Chinese WD patients. Methods One hundred three WD patients from 101 unrelated families in southern China were enrolled in this study. Genomic DNA was extracted from the peripheral blood. Direct sequencing of all 21 exons within ATP7B was performed. Subsequently, an extensive study of the overall spectrum and frequency of ATP7B mutations and genotype–phenotype correlation was performed in all Chinese patients eligible from the literature, combined with the current southern group. Results In 103 patients with WD, we identified 48 different mutations (42 missense mutations, 4 nonsense mutations and 2 frameshifts). Of these, 3 mutations had not been previously reported: c.1510_1511insA, c.2233C>A (p.Leu745Met) and c.3824T>C (p.Leu1275Ser). The c.2333G>T (p.Arg778 Leu) at exon 8, was the most common mutation with an allelic frequency of 18.8%, followed by c.2975C>T (p.Pro992Leu) at exon 13, with an allelic frequency of 13.4%. In the comprehensive study, 233 distinct mutations were identified, including 154 missense mutations, 23 nonsense mutations and 56 frameshifts. Eighty-five variants were identified as novel mutations. The c.2333G>T (p.Arg778 Leu) and c.2975C>T (p.Pro992Leu) were the most common mutations, with allelic frequencies of 28.6% and 13.0%, respectively. Exons 8, 12, 13, 16 and 18 were recognised as hotspot exons. Phenotype–genotype correlation analysis suggested that c.2333G>T (p.Arg778 Leu) was significantly associated with lower levels of serum ceruloplasmin (P = 0.034). c.2975C>T (p.Pro992Leu) was correlated with earlier age of disease onset (P = 0.002). Additionally, we found that the c.3809A>G (p.Asn1270Ser) mutation significantly indicated younger onset age (P = 0.012), and the c.3884C>T (p.Ala1295Val) mutation at exon 18 was significantly associated with hepatic presentation (P = 0.048). Moreover, the patients with mixed presentation displayed the initial WD features at an older onset age than the groups with either liver disease or neurological presentation (P = 0.039, P = 0.015, respectively). No significant difference was observed in the presence of KF rings among the three groups with different clinical manifestations. Conclusion In this study, we identified three novel mutations in 103 WD patients from the southern part of China, which could enrich the previously established mutational spectrum of the ATP7B gene. Moreover, we tapped into a large-scale study of a Chinese WD cohort to characterise the overall phenotypic and genotypic spectra and assess the association between genotype and phenotype, which enhances the current knowledge about the population genetics of WD in China.

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Section: Characterisation Of Clinical Phenotypementioning

confidence: 99%

Mutation analysis of the ATP7B gene and genotype–phenotype correlation in Chinese patients with Wilson disease

Wen-long

et al. 2021

BMC Gastroenterol

View full text Add to dashboard Cite

show abstract

“…Screening patients from the 14 eligible reports [14][15][16][17][18][19][20][21][22][23][24][25][26][27] identi ed 108 patients with clear WD features. We enrolled 196 patients with WD in the nal analysis, including the current 88 patients with detailed data from southern China.…”

Section: Characterisation Of Clinical Phenotypementioning

confidence: 99%

Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese patients with Wilson disease

Wang

et al. 2021

Preprint

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AIM To discover the novel ATP7B mutations in 103 southern Chinese patients with Wilson disease (WD), and to determine the spectrum and frequency of mutations in the ATP7B gene and genotype-phenotype correlation in a large-scale sample of Chinese WD patients. Methods One hundred three WD patients from 101 unrelated families in southern China were enrolled in this study. Genomic DNA was extracted from the peripheral blood. Direct sequencing of all 21 exons within ATP7B was performed. Subsequently, an extensive study of the overall spectrum and frequency of ATP7B mutations and genotype-phenotype correlation was performed in all Chinese patients eligible from the literature, combined with the current southern group.Results In 103 patients with WD, we identified 48 different mutations (42 missense mutations, 4 nonsense mutations and 2 frameshifts). Of these, 7 mutations had not been previously reported: 1510_1511insA, 2075T>C (Leu692Pro), 2233C>A (Leu745Met), 3209C>G (Pro1070Arg),3677C>T (Thr1226Ile), 3793G>T (Val1265Leu) and 3824T>C (Leu1275Ser). The 2333G>T (Arg778 Leu) at exon 8, was the most common mutation with an allelic frequency of 18.8%, followed by 2975C>T (Pro992Leu) at exon 13, with an allelic frequency of 13.4%. In the comprehensive study, 233 distinct mutations were identified, including 154 missense mutations, 23 nonsense mutations and 56 frameshifts. Eighty-five variants were identified as novel mutations. The 2333G>T (Arg778 Leu) and 2975C>T (Pro992Leu) were the most common mutations, with allelic frequencies of 28.6% and 13.0%, respectively. Exons 8, 12, 13, 16 and 18 were recognised as hot spot exons. Phenotype-genotype correlation analysis suggested that 2333G>T (Arg778 Leu) was significantly associated with lower levels of serum ceruloplasmin (P=0.034). 2975C>T (Pro992Leu) was correlated with earlier age of disease onset (P=0.002). Additionally, we found that the 3809A>G (Asn1270Ser) mutation significantly indicated younger onset age (P=0.012), and the 3884C>T (Ala1295Val) mutation at exon 18 was significantly associated with hepatic presentation (P=0.048). Moreover, the patients with mixed presentation displayed the initial WD features at an older onset age than the groups with either liver disease or neurological presentation (P=0.039, P=0.015, respectively). No significant difference was observed in the presence of KF rings among the three groups with different clinical manifestations. Conclusion In this study, we identified seven novel mutations in 103 WD patients from the southern part of China, which could enrich the previously established mutational spectrum of the ATP7B gene. Moreover, we tapped into a large-scale study of a Chinese WD cohort to characterise the overall phenotypic and genotypic spectra and assess the association between genotype and phenotype, which enhances the current knowledge about the population genetics of WD in China.

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Identification of two novel mutations in the ATP7B gene that cause Wilson’s disease

Abstract: Gene testing is playing an important role in diagnosis of Wilson's disease. The early-onset of Wilson's disease is apparently not associated with P-ATPase domain in the ATP7B protein. Our findings further widen the spectrum of mutations involving the ATP7B gene.

Cited by 2 publications

References 20 publications

Mutation analysis of the ATP7B gene and genotype–phenotype correlation in Chinese patients with Wilson disease

Mutation analysis of the ATP7B gene and genotype–phenotype correlation in Chinese patients with Wilson disease

Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese patients with Wilson disease

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