Butler P, McIntyre N, Mistry P K
Department of Medicine, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, Hampstead, London NW3 2PF, United Kingdom.
Mol Genet Metab. 2001 Mar;72(3):223-30. doi: 10.1006/mgme.2000.3143.
Wilson disease (WD) is caused by mutations in the ATP7B gene. The diagnosis is based on clinical and biochemical criteria but these are increasingly recognized to have low sensitivity. Genetic diagnosis is considered impractical due to the large coding region of the ATP7B gene and extreme diversity of mutations. We assessed the feasibility and utility of genetic diagnosis in WD. The coding region of the ATP7B gene was scanned by single-stranded conformation polymorphism (SSCP) analysis in 6 cases in whom the diagnosis of WD was uncertain. In addition, we attempted molecular diagnosis in 26 WD patients of similar ethnicity but variable disease manifestations. In 6 individuals in whom the biochemical/clinical diagnosis was uncertain, DNA analyses were useful for assigning their status with respect to WD. Molecular diagnosis identified presymptomatic individuals in families affected by WD and assigned heterozygote carrier or wild-type status to individuals previously diagnosed as affected. In 26 WD patients, 92% of disease alleles were identified. The most common mutations were H1069Q, L936X, and 2532delA representing 48, 10, and 8% of disease alleles, respectively. Three novel mutations were identified: Q898R, 3061(-1)g --> a, and 3972insC. Genetic diagnosis is feasible for WD. Greater application of molecular diagnosis should enable an appreciation of the full spectrum of WD phenotype that is not possible with currently available diagnostic criteria.
威尔逊病（WD）由ATP7B基因突变引起。诊断基于临床和生化标准，但这些标准的敏感性越来越被认为较低。由于ATP7B基因编码区大且突变极其多样，基因诊断被认为不切实际。我们评估了WD基因诊断的可行性和实用性。对6例WD诊断不确定的患者，通过单链构象多态性（SSCP）分析扫描ATP7B基因的编码区。此外，我们对26例种族相似但疾病表现各异的WD患者进行了分子诊断。在6例生化/临床诊断不确定的个体中，DNA分析有助于确定他们与WD相关的状态。分子诊断在受WD影响的家庭中识别出症状前个体，并将杂合子携带者或野生型状态赋予先前被诊断为患病的个体。在26例WD患者中，92%的致病等位基因被识别。最常见的突变是H1069Q、L936X和2532delA，分别占致病等位基因的48%、10%和8%。还识别出三个新突变：Q898R、3061（-1）g→a和3972insC。WD的基因诊断是可行的。更广泛地应用分子诊断应能全面了解WD的表型谱，而这是目前可用诊断标准无法做到的。
