Genetic analysis of 3 pedigrees with autosomal dominant polycystic kidney disease

Abstract

Objective To clarify the pathogenic mutations and provide references for prevention and treatment strategies and prenatal diagnosis by gene detection in 3 pedigrees with autosomal dominant polycystic kidney disease (ADPKD). Methods The family history and clinical data of 3 ADPKD pedigrees who admitted to our department of urology during 2017 and 2020 were collected in this study. The peripheral blood samples of these family members were harvested for DNA extraction. Targeted amplification and high-throughput sequencing was used to screen suspected pathogenic mutations in probands, and then these obtained mutations were verified and analyzed in the probands and their family members by Sanger sequencing. The pathogenicity of these mutations was analyzed with bioinformation analysis and the evaluation criteria of the American Society of Medical Genetics. Results Ultrasound examination showed that all the probands from the 3 families had polycystic kidneys, at the clinical stages of G1, G3a, and G5 respectively. The deletion frameshift mutation c.5933delA (p.Asn1978fs), nonsense heterozygous mutation c.6871C>T (G2291X) and deletion frameshift mutation of c.894_897delCCCT (p.299Sfs*34) in polycystic kidney disease 1 (PKD1) gene were detected in pedigrees 1, 2 and 3, respectively. The above variants in the 3 families were in line with phenotype-genotype separation. Conclusion We identify the pathogenic variants in the 3 pedigrees of hereditary polycystic kidney disease, among which c.5933delA and c.894_897delCCCT are new mutations, and c.6871C>T is a known pathogenic mutation.

Keywords

• autosomal dominant
• polycystic kidney
• pkd1 gene
• gene variation