Comprehensive PKD1 and PKD2 mutation analysis in prenatal autosomal dominant polycystic kidney disease

Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, andPKHD1 associated with the familialPKDmutation in earlyADPKD, these four geneswere screened in 42 patients with earlyADPKD in 41 families. Two patientswere associatedwith de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%,P=0.001)patientswith adultADPKD.NoHNF1Bvariations or PKHD1biallelicmutationswere identified.These results suggestthat,at least insomepatients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.