Genetic and Clinical Analysis in a Cohort of Patients with Wilson's Disease in Southwestern China

Liu, Yu; Zhou, Hao; Guo, Hong; Bai, Yun

doi:10.1016/j.arcmed.2015.02.001

Cited by 9 publications

(7 citation statements)

References 18 publications

(27 reference statements)

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“…The mutation p.R778L has been reported as the most common mutation of the ATP7B gene in Asians. (Li et al, ; Liu, Zhou, Guo, & Bai, ; Mak et al, ; Tsai et al, ; Wu et al, ). Our study also indicated that p.R778L is the most frequent mutation with allelic frequency of 14.5%, followed by p.P992L and p.I1148T (13.2 and 10.1%).…”

Section: Discussionmentioning

confidence: 99%

Clinical features and mutational analysis in 114 young children with Wilson disease from South China

Lin

et al. 2019

American J of Med Genetics Pt A

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Wilson disease (WD) is a rare autosomal recessive disorder caused by mutations in the ATP7B gene. Clinical features and mutational analysis of Chinese children with WD at early age were rarely described. Herein, we retrospectively examined 114 children with WD at the mean of 5.9 years old age at diagnosis. Eight patients developed acute liver failure at mean age of 9.7 years old, 4 of whom died. Among the 114 patients, 86.0%were presymptomatic with isolated elevation of transaminases at diagnosis, 99.1% had decreased ceruloplasmin, and 68.4% had urinary copper excretion over 100 μg/24 hr.Bi-allele pathogenic ATP7B mutations were identified in all patients. Among the 60 mutations detected, 10 were novel, including 7 missense mutations (p.I566N, p.

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Section: Discussionmentioning

confidence: 99%

Clinical features and mutational analysis in 114 young children with Wilson disease from South China

Lin

et al. 2019

American J of Med Genetics Pt A

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“…In a study reported by Lee BH et al from Korea, [ 21 ] none of 237 patients with WD had normal CP levels. In a study reported by Feng L et al from China, [ 22 ] none of 126 patients with WD had normal CP levels, and in another study reported by Liu Y et al from China,[ 23 ] one of 57 patients with WD had normal CP levels [ Table 6 ]. Therefore, we speculated that some unclear regional factors from China and Korea contributed to this discrepancy.…”

Section: Discussionmentioning

confidence: 99%

The optimal threshold of serum ceruloplasmin in the diagnosis of Wilson’s disease: A large hospital-based study

Jiang

Zhang

et al. 2018

PLoS ONE

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Background and aimsA ceruloplasmin (CP) concentration <200 mg/L is conventionally considered as one of the major diagnostic criteria for Wilson’s disease (WD). However, the diagnostic accuracy of this threshold has never been investigated in a sufficiently large group of patients. This study aims to present the results of serum CP measurements in various patients and to identify the optimal cutoff value of CP for the diagnosis of WD.Materials and methodsWe identified patients whose CP levels were evaluated from January 1, 2016 to December 31, 2016 using a laboratory information database. Data related to CP measurement were retrieved. We carefully reviewed patients’ electronic medical records to correct errors and to obtain other necessary data. Data related to WD were retrieved from a special document containing medical records of patients with WD, which were created, modified, and maintained by authors.ResultsCP level was determined in 4048 patients (WD, 297; non-WD, 3751). The mean serum CP level in patients with WD was 50.6±44.2 mg/L, which was significantly lower than that in non-WD patients (293.2±117.3 mg/L, p<0.001). Only 1.0% of patients with WD had CP ≥200 mg/L. The sensitivity and specificity of CP for the diagnosis of WD were 99.0 and 80.9%, respectively, for the conventional cutoff value <200 mg/L and 95.6 and 95.5%, respectively, for the cutoff value <150 mg/L; the latter provided a higher diagnostic accuracy for WD. 53.0% of patients with liver failure, 37.7% of patients with nephrotic syndrome, and 23.0% of patients age 1 to 6 months had serum CP <200 mg/L. Patients who were pregnant and those with malignant tumors, and infectious and inflammatory diseases had significantly higher mean serum CP levels.ConclusionThe optimal cutoff value of CP for the diagnosis of WD in China is 150 mg/L, with a sensitivity of 95.6% and specificity of 95.5%, thereby providing the highest diagnostic accuracy for WD.

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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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Genetic and Clinical Analysis in a Cohort of Patients with Wilson's Disease in Southwestern China

Cited by 9 publications

References 18 publications

Clinical features and mutational analysis in 114 young children with Wilson disease from South China

Clinical features and mutational analysis in 114 young children with Wilson disease from South China

The optimal threshold of serum ceruloplasmin in the diagnosis of Wilson’s disease: A large hospital-based study

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

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