Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease
Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease
复制标题
DOI：
10.1038/ng1104
复制
发表时间：
2003-03-01
期刊：
影响因子：
30.8
通讯作者：
Jansen, JBMJ
中科院分区：
文献类型：
--
作者：
Drenth, JPH;Morsche, RHMT;Jansen, JBMJ
多囊肝病（PCLD，OMIM 174050）是一种显性遗传性疾病，其特征是存在多个胆管上皮起源的肝囊肿。精细定位在4个荷兰PCLD大家族中建立了与标记D19 S581（Z（max）=9.65; theta=0.01）的连锁。我们在3个家系中发现了PRKCSH的一个剪接受体位点突变（1138-2A-->G），在另一个家系中发现了PRKCSH的一个剪接供体位点突变（292+1G-->C），该突变与PCLD完全分离。由PRKCSH编码的蛋白质，在此命名为hepatocystin，被预测定位于内质网。这些发现确定PRKCSH的种系突变是PCLD的可能原因。
Polycystic liver disease (PCLD, OMIM 174050) is a dominantly inherited condition characterized by the presence of multiple liver cysts of biliary epithelial origin. Fine mapping established linkage to marker D19S581 (Z(max)=9.65; theta=0.01) in four large Dutch families with PCLD. We identified a splice-acceptor site mutation (1138-2A-->G) in PRKCSH in three families, and a splice-donor site mutation (292+1G-->C) in PRKCSH segregated completely with PCLD in another family. The protein encoded by PRKCSH, here named hepatocystin, is predicted to localize to the endoplasmic reticulum. These findings establish germline mutations in PRKCSH as the probable cause of PCLD.