Yang Wenming, Yang Yue, Wang Han, Wang Jiuxiang, Zhang Shijie
Department of Neurology, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.
Experimental Center of Clinical Research, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.
NPJ Genom Med. 2024 Dec 24;9(1):71. doi: 10.1038/s41525-024-00459-z.
Wilson's disease (WD) typically manifests in children and young adults, with little knowledge of its late-onset forms. In this study, we performed a retrospective cohort study of 105 WD patients (99 index cases, 6 siblings) with an onset age ≥35 years. We compared 99 index late-onset patients with 1237 early-onset patients and analyzed the ATP7B variant penetrance referring to the Genome Aggregation Database (gnomAD). Sixty-two ATP7B variants were identified in the late-onset patients, among which A874V, V1106I, R919G, and T935M were correlated with late presentation of WD. Regarding gnomAD, V1106I and T935M exhibited significantly low penetrance, and there is a lack of patients carrying a genotype of V1106I/V1106I, R919G/R919G, T935M/T935M, V1106I/T935M, V1106I/R919G, or T935M/R919G. Our data revealed that patients carrying a combination of two late-onset variants may be overlooked due to atypical or lack of WD symptoms, which may provide valuable insights into the genetic basis and diagnosis of WD.
威尔逊病（WD）通常在儿童和年轻人中表现出来，对其迟发型形式了解甚少。在本研究中，我们对105例发病年龄≥35岁的WD患者（99例索引病例，6例同胞）进行了回顾性队列研究。我们将99例迟发型索引患者与1237例早发型患者进行了比较，并参考基因组聚合数据库（gnomAD）分析了ATP7B变异外显率。在迟发型患者中鉴定出62种ATP7B变异，其中A874V、V1106I、R919G和T935M与WD的迟发表现相关。关于gnomAD，V1106I和T935M表现出显著低外显率，并且缺乏携带V1106I/V1106I、R919G/R919G、T935M/T935M、V1106I/T935M、V1106I/R919G或T935M/R919G基因型的患者。我们的数据显示，携带两种迟发型变异组合的患者可能因非典型或缺乏WD症状而被忽视，这可能为WD的遗传基础和诊断提供有价值的见解。
