Extensive mutational analysis of PRKCSH and SEC63 broadens the spectrum of polycystic liver disease.
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.
Waanders
Esmé
E
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. e.waanders@mdl.umcn.nl
te Morsche
René H M
RH
de Man
Rob A
RA
Jansen
Jan B M J
JB
Drenth
Joost P H
JP
D002135:Calcium-Binding Proteins; D018389:Codon, Nonsense; D015331:Cohort Studies; D003560:Cysts / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D005959:Glucosidases; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008107:Liver Diseases / Q000175:diagnosis* / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D018832:Molecular Chaperones; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D016601:RNA-Binding Proteins
D002135:Calcium-Binding Proteins; D018389:Codon, Nonsense; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; C487464:SEC63 protein, human; D005959:Glucosidases; C070368:PRKCSH protein, human