Clinical characteristics and genetic features of patients with Wilson's disease in southwestern China.

backgroundWilson's disease (WD) is a rare autosomal recessive disorder caused by mutations in the ATP7B gene, leading to copper metabolism dysfunction. The clinical and genetic manifestations of WD vary across populations. This study aimed to characterize the clinical features and genetic mutations in WD patients from southwestern China and to explore genotype-phenotype correlations.

methodsA total of 120 WD patients from southwestern China were included. Clinical data were collected through face-to-face interviews and medical record reviews. ATP7B mutations were identified through whole-genome resequencing. Genotype-phenotype correlations were analyzed in patients with pathogenic mutations on both alleles.

resultsAmong the 120 WD patients, the median age at onset was 17 years (range 3 to 49 years), with neurological symptoms being the most common initial presentation (61.7%). At the time of enrollment, the median disease duration was 10 years, with persistent neurological symptoms commonly observed, and 62.5% of patients had progressed to cirrhosis. Sex and age differences in clinical characteristics were also observed. In the analysis of ATP7B gene mutations, a total of 47 distinct pathogenic mutations were identified, including 32 missense, 6 nonsense, 6 frameshift, and 3 splicing mutations. The most prevalent mutations were c.2333G > T (p.R778L) and c.2975 C > T (p.P992L). Notably, one novel pathogenic frameshift mutation, c.386delA (p.K129Rfs*24), and another novel variant of uncertain significance, c.1987 C > A (p.P663T), were identified. Among the 117 unrelated patients, 98 (83.8%) had pathogenic mutations on both alleles, with 62 different mutation combinations observed. Genotype-phenotype analysis showed that p.R778L, p.P992L, and loss-of-function (LOF) mutations were not significantly associated with the initial clinical subtype, whereas p.R778L was associated with a later age at onset and LOF mutations with an earlier age at onset.

conclusionThis study provided some valuable insights into the clinical and genetic characteristics of WD in southwestern China, enhanced the understanding of genotype-phenotype correlations, and emphasized the importance of early diagnosis and personalized management.