Mutational screening of PKD1 and PKD2 in Indian ADPKD patients identified 95 genetic variants

Abstract

Background: Mutation screening of autosomal dominant polycystic kidney disease (ADPKD) cases imply the major involvement of PKD1 mutations in 85% of patients while rest of the cases harbor mutation in PKD2, DNAJB11 and GANAB. This essentially indicates that individual's genotype holds the key for disease susceptibility and its severity.

Methods: For finding genetic variability underlying the disease pathophysiology, 84 Indian ADPKD cases, 31 family members (12 susceptible) and 122 age matched control were screened for PKD1 and PKD2 using Sanger sequencing, PCR-RFLP and ARMS-PCR.

Results: Genetic screening of Indian ADPKD cases revealed total 67 variants in PKD1 and 28 variants in PKD2. Among the identified variants in PKD1 and PKD2 genes, 35.79% were novel variants and 64.2% recurrent. Further, subcategorization of PKD1 variants showed 14 truncation/frameshift, 21 nonsynonymous, 25 synonymous and 7 intronic variants. Moreover, we observed 40 families with PKD1 pathogenic variants, 7 families with PKD2 pathogenic variants, 9 families with PKD1 & PKD2 pathogenic variants, and 26 families with PKD1/PKD2/PKD1-PKD2 non-pathogenic genetic variants.

Conclusion: Present study represented genetic background of Indian ADPKD cases which will be helpful in disease management as well as finding the genetically matched donor for kidney transplant.

Keywords: Familial ADPKD cases; Haplotype; Novel PKD mutations; Pathogenic variants; Private mutation; Trucncated mutation.