Thomas G R, Forbes J R, Roberts E A, Walshe J M, Cox D W
Research Institute, Hospital for Sick Children, Toronto, Canada.
Nat Genet. 1995 Feb;9(2):210-7. doi: 10.1038/ng0295-210.
We have previously reported the cloning of a gene that encodes a copper transporting P-type ATPase (ATP7B) which is defective in Wilson disease. We have now identified in 58 WND patients, 20 new mutations as well as three of five previously published mutations: 11 small insertions and deletions, seven missense, two nonsense and three splice site mutations. Two of the mutations are relatively frequent, representing 38% of the mutations in patients of European origin. Our findings suggest a wider spectrum of age of onset than is considered typical of Wilson disease: mutations that completely disrupt the gene can produce liver disease in early childhood when Wilson disease may not typically considered in the differential diagnosis. The mutations identified provide an explanation for at least part of the wide phenotypic variation observed in Wilson disease.
我们之前报道过克隆出一个编码铜转运P型ATP酶（ATP7B）的基因，该基因在威尔逊病中存在缺陷。我们现已在58例威尔逊病患者中鉴定出20个新突变以及之前公布的5个突变中的3个：11个小插入和缺失、7个错义突变、2个无义突变和3个剪接位点突变。其中两个突变相对常见，在欧洲裔患者的突变中占38%。我们的研究结果表明，威尔逊病的发病年龄范围比通常认为的要更广：完全破坏该基因的突变可在儿童早期引发肝病，而此时威尔逊病通常不在鉴别诊断范围内。所鉴定出的突变至少部分解释了威尔逊病中观察到的广泛表型变异。
