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Extensive mutational analysis of PRKCSH and SEC63 broadens the spectrum of polycystic liver disease
Author(s) -
Waanders Esmé,
te Morsche René H.M.,
de Man Rob A.,
Jansen Jan B.M.J.,
Drenth Joost P.H.
Publication year - 2006
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9441
Subject(s) - biology , polycystic liver disease , genetics , computational biology , disease , bioinformatics , medicine , transplantation , liver transplantation
Autosomal dominant polycystic liver disease (PCLD) is characterized by progressive development of multiple (>20) liver cysts. Two separate genes, PRKCSH and SEC63 , have been identified to cause familial PCLD. We designed this study with two goals: to assess the relative contribution of PRKCSH and SEC63 mutations in a cohort of unrelated patients with a variable number of liver cysts, and to assess the effect of these mutations on the severity of the PCLD phenotype. We selected patients with two or more liver cysts on radiological studies and excluded those with renal cysts. A total of 51 patients entered the study and three groups were distinguished: A, 2‐10 cysts (18 patients); B, 11‐20 cysts (nine patients); and C, more than 20 cysts (24 patients). In total we found that eight patients with multiple liver cysts (16%) had PRKCSH (5) or SEC63 (3) mutations. Two patients (11%) from group A had missense mutations (1 PRKCSH and 1 SEC63 ). Six patients (25%) with more than 20 liver cysts had mutations (4 PRKCSH and 2 SEC63 ), of which five mutations were chain‐terminating. In conclusion, both PRKCSH and SEC63 mutations are associated with polycystic liver disease. Frequency and severity of mutations is higher among patients with more than 20 liver cysts, but also patients with as few as eight liver cysts can be mutation carriers. © 2006 Wiley‐Liss, Inc.