关键词: 常染色体显性遗传性多囊肾, PKD1基因, PKD2基因, 突变

Abstract:

Abstract Objective: To analysis and identify mutations of PKD1, PKD2 gene in a Chinese family with Autosomal dominant polycystic kidney disease (ADPKD). Methodology: To determine the genetic defects in proband with ADPKD by next-generation sequencing to capture exons of PKD1, PKD2 gene. Then, specific mutations of the 8 family members were detected by Sanger DNA sequencing, and the SIFT and Polyphen software were applied for protein function prediction about mutations. Results: The heterozygous frame shift mutation c.2085_2086insC (p.Ala696Argfs17X) in exon Tenth of PKD1 gene was detected, which mutation caused amino acid code code early termination. The finding two missense mutations (p.Ala1447Val, P.Arg739Gln) were harmless in PKD1 gene on prediction of protein function. Furthermore, the additional two synonymous mutations (p.Leu373Leu, p.Asn890Asn) in PKD1 gene were identified. The coding region of PKD2 gene was not found frameshift, nonsense, shear, or synonymous mutations. The p.Ala696Argfs17X mutation was found in the other ADPKD family members, and was not found in normal members. Conclusion: We hypothesized that frame shift mutation (p.Ala696Argfs17X) in the PKD1 gene was suspicious pathogenic mutations in this family.

Key words: autosomal dominant polycystic kidney disease, PKD1 gene , PKD2 gene , mutation