Gastroenterology and Hepatology Center, Fundeni Clinical Institute, University of Bucharest, Romania.
J Gastrointestin Liver Dis. 2012 Jun;21(2):181-5.
Wilson's disease (WD) is a rare autosomal recessive disease. More than 500 mutations have been described so far, out of which 29 in exon 14. H1069Q mutation in the exon 14 of ATP7B gene is the most frequently encountered in Europe. The aim of the present study was to evaluate the incidence of mutations occurring in exon 14 of ATP7B gene in Romanian patients referred to a tertiary gastroenterology center, with known or suspected WD and in asymptomatic first degree relatives of index cases.
93 patients were included in the study. Exon 14 of ATP7B gene has been amplified by PCR from genomic DNA and mutations identified by sequencing.
Only H1069Q missense mutation was detected in our study group. In patients with an established diagnosis of WD (38 cases), 34.2% were heterozygous for H1069Q and 21.1% were homozygous, with an allelic frequency of 38.1%. In paediatric WD patients (12 cases) 25% were heterozygous and 16.7% were homozygous (not significant versus adult population). Among asymptomatic first degree relatives of patients with WD (12 siblings, 25 parents) there were 40.5% cases heterozygous for H1069Q. In patients with suspected WD (17 cases), only 5.9% were heterozygous and no homozygous patient was identified. In our study group, H1069Q screening alone could not raise the Leipzig score to confirm diagnosis in patients with suspected WD or in asymptomatic first degree relatives.
H1069Q mutation is highly prevalent in Romanian WD patients and first degree relatives, similar to other central and continental western European populations.
Wilson 病（WD）是一种罕见的常染色体隐性遗传病。迄今为止，已经描述了超过 500 种突变，其中 29 种发生在外显子 14 中。ATP7B 基因外显子 14 中的 H1069Q 突变在欧洲最为常见。本研究旨在评估罗马尼亚一家三级胃肠病学中心就诊的、已知或疑似 WD 患者以及索引病例一级无症状亲属中发生在外显子 14 的 ATP7B 基因突变的发生率。
本研究共纳入 93 例患者。采用 PCR 从基因组 DNA 中扩增 ATP7B 基因外显子 14，并通过测序鉴定突变。
在我们的研究组中仅检测到 H1069Q 错义突变。在已确诊 WD 的患者（38 例）中，34.2%为 H1069Q 杂合子，21.1%为纯合子，等位基因频率为 38.1%。在儿童 WD 患者（12 例）中，25%为杂合子，16.7%为纯合子（与成人人群无显著差异）。在 WD 患者的一级无症状亲属中（12 个兄弟姐妹，25 个父母），有 40.5%的病例为 H1069Q 杂合子。在疑似 WD 患者（17 例）中，仅 5.9%为杂合子，未发现纯合子患者。在本研究组中，单独进行 H1069Q 筛查无法提高莱比锡评分以确认疑似 WD 患者或无症状一级亲属的诊断。
H1069Q 突变在罗马尼亚 WD 患者及其一级亲属中非常普遍，与其他中欧和西欧大陆人群相似。
