Pathogenicity analysis of a novel PKD1 mutation in a pedigree of autosomal dominant polycystic kidney disease

Objective To identify pathogenic mutations underlying polycystic kidney disease(PKD)in a pedigree, and provide genetic counseling and reproductive guidance. Methods Whole exome sequencing was used to detect the pathogenic mutation of the proband, and Sanger sequencing was used to verify the pathogenic mutation in this pedigree. The pathogenicity of the novel mutation was identified in combination with the clinical manifestations of the proband’s family and the ACMG/AMP guidelines. Results PKD patients in this family have PKD1 c. 6079delA (p.Thr2027fs), a heterozygous transcoding mutations. According to the ACMG/AMP guidelines, the mutation was classified as "pathogenic" with one " very strong" pathogenic evidence(PVS1), one " moderate" pathogenic evidence (PM2) and two " supporting evidence" (PP3, PP4). Conclusion The discovery of a novel pathogenic mutation PKD1 c. 6079delA enriched the gene mutation spectrum of PKD1 and provided a basis for genetic counseling and genetic diagnosis in this pedigree. Our finding above could guide asymptomatic family members and prevent renal failure. Key words: Autosomal dominant polycystic kidney disease; PKD1 gene; Pathogenic novel mutation; Whole exome sequencing