Houwen R H, Roberts E A, Thomas G R, Cox D W
Research Institute, Hospital for Sick Children, Toronto, Canada.
J Hepatol. 1993 Mar;17(3):269-76. doi: 10.1016/s0168-8278(05)80204-1.
Wilson disease is an autosomal recessive disorder of copper transport for which the basic defect is unknown. Laboratory diagnosis of Wilson disease is usually made by measuring serum ceruloplasmin concentration, urinary copper excretion, and liver copper concentration. However, discrimination between heterozygotes and patients is sometimes difficult. The gene for Wilson disease has been assigned to chromosome-13 at q14-q21. In this study, 10 markers from the 13q14-13q21 region were investigated in 12 families with a well-established diagnosis, to confirm reported linkage results. Markers from the same region were tested in two additional families, in which a sib of each index case had unclear results with conventional biochemical assays. The linkage results in this study are similar to those of Middle Eastern families, and support the hypothesis of a single disease locus. In the two families studied for diagnostic purposes, the status of 2 presymptomatic sibs was established as affected and 1 as unaffected. This study therefore shows that DNA markers can be used to discriminate between presymptomatic patients and non-affected individuals when biochemical results are equivocal, as long as an index case with Wilson disease of known status is available and markers are informative.
威尔逊病是一种常染色体隐性铜转运障碍疾病，其基本缺陷尚不清楚。威尔逊病的实验室诊断通常通过测量血清铜蓝蛋白浓度、尿铜排泄量和肝铜浓度来进行。然而，有时很难区分杂合子和患者。威尔逊病基因已被定位于13号染色体的q14 - q21区域。在本研究中，对12个诊断明确的家庭中的13q14 - 13q21区域的10个标记进行了研究，以确认已报道的连锁结果。在另外两个家庭中测试了来自同一区域的标记，在这两个家庭中，每个索引病例的一个同胞通过传统生化检测结果不明确。本研究中的连锁结果与中东家庭的结果相似，并支持单一疾病位点的假说。在为诊断目的而研究的两个家庭中，2名症状前同胞的状态被确定为患病，1名被确定为未患病。因此，本研究表明，只要有已知状态的威尔逊病索引病例且标记具有信息性，当生化结果不明确时，DNA标记可用于区分症状前患者和未受影响个体。
