Laboratoire de génétique moléculaire, pharmacogénétique, hormonologie, université Paris Sud, hôpital Bicêtre, AP-HP, 94270 Le Kremlin-Bicêtre, France.
Clin Res Hepatol Gastroenterol. 2013 Jun;37(3):240-5. doi: 10.1016/j.clinre.2013.01.001. Epub 2013 Apr 6.
Wilson disease (WD) is an autosomal recessive genetic disorder caused by mutations in the ATP7B gene resulting in toxic accumulation of copper mainly in the liver and brain. Early treatment may prevent irreversible tissue damage.
We report on four families with an occurrence of WD in two consecutive generations in order to highlight the need for screening offspring of affected parents.
In all families, one parent was known to be affected with WD. Screening for the disease was not performed in children from two families until occurrence of liver disease in one and of neurological symptoms in the other. In two other families, screening of children as soon as diagnosis was performed in the affected parent allowed a timely rescue of advanced liver disease in one while two affected children were asymptomatic. In three children, diagnosis required direct sequencing of the ATP7B gene. Two novel disease-causing mutations are reported.
Patients with WD should be offered genetic counselling when considering pregnancy and offspring should always be screened for the disease. Diagnostic difficulties based on copper disturbances in asymptomatic children that are obligate carriers of the Wilson gene and the usefulness of molecular diagnosis are discussed.
威尔逊病（WD）是一种常染色体隐性遗传疾病，由 ATP7B 基因突变引起，导致铜在肝脏和大脑中的毒性蓄积。早期治疗可能预防不可逆的组织损伤。
我们报告了四个 WD 在连续两代人中发生的家族，以强调对受影响父母后代进行筛查的必要性。
在所有家族中，已知有一位父母患有 WD。直到其中一个家族的孩子出现肝脏疾病，另一个家族的孩子出现神经症状，才对两个家族的孩子进行了疾病筛查。在另外两个家族中，一旦对受影响的父母进行诊断，就对孩子进行筛查，及时挽救了一个孩子的晚期肝病，而两个受影响的孩子无症状。在三个孩子中，诊断需要直接对 ATP7B 基因进行测序。报告了两个新的致病突变。
当考虑怀孕时，应向 WD 患者提供遗传咨询，并且应始终对后代进行疾病筛查。讨论了基于无症状儿童铜紊乱的诊断困难，这些儿童是威尔逊基因的强制性携带者，以及分子诊断的有用性。
