Novel Mutations in the PKD1 and PKD2 Genes of Chinese Patients with Autosomal Dominant Polycystic Kidney Disease

Abstract

Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder with mutations in PKD1 or PKD2. This study aimed to identify novel PKD1 and PKD2 mutations in Chinese patients with ADPKD. Methods: Mutational analyses of both PKD genes were performed in 120 Chinese families with inherited ADPKD using long-range PCR and targeted next-generation sequencing approaches. Sanger sequencing was performed to check the positive mutations, while multiplex ligation-dependent probe amplification was adopted to examine those without mutations for the presence of large deletions. Results: A total of 93 mutations in PKD1 and PKD2 were identified in 98 Chinese families with ADPKD inheritance and the detection rate was 81.7% (98/120). The mutation rates of PKD1 and PKD2 were 91.4% (85/93) and 8.6% (85/93), respectively. Among the 93 mutations, 59.1% (55/93) were reported for the first time. A total of 65 mutations (26 nonsense, 33 frameshift, 2 large deletion, and 4 typical splicing mutations) were identified as definite pathogenic mutations. The remaining 28 mutations (21 missense, 3 in-frame deletion, and 4 atypical splicing mutations) were determined as probable pathogenic mutations. In addition, 9 de novo mutations were found by pedigree analysis. Correlation analysis between genotype and phenotype revealed that patients with PKD1 mutations or truncating mutations exhibited the most severe clinical outcome. Conclusion: The newly identified sites for known mutations will facilitate the early diagnosis and prediction of prognosis in patients with ADPKD, and provide fundamental genetic information for clinical intervention to prevent the inheritance of this disease in affected families.

The genetics of situs inversus without primary ciliary dyskinesia

“…(2020) 10:3677 | https://doi.org/10.1038/s41598-020-60589-z www.nature.com/scientificreports www.nature.com/scientificreports/ We note possible compound heterozygous mutations in PKD1 [MIM:601313], as a paralogue of PKD1L1 [MIM:609721], in subject SI14 ( Supplementary Table S3). However, mutations in this gene would be expected to cause autosomal dominant Polycystic Kidney Disease 63,64 , and since there was no such diagnostic record for this subject, one or both of these specific mutations probably has limited functional impact and is therefore unlikely to be a monogenic cause for SI either. As noted above, SI14 anyway had likely causative mutations in CFAP52.…”

A novel frameshift PKD1 mutation in a Chinese patient with autosomal dominant polycystic kidney disease and azoospermia: A case report

“…Due to the long range and the six pseudogenes, single-molecule long-read sequencing is more suitable for the detection of genetic variants in patients with ADPKD (24)(25)(26). In the present study, long-range PCR (LR-PCR) amplification and targeted next-generation sequencing, as described previously (27), was used to detect the variants of PKD1 and PKD2 in the 33-year-old male patient. No PKD2 mutation was identified; however, a T-allele deletion causing a frameshift mutation was identified at the 9,053th position of PKD1 complementary DNA.…”

PKD2 gene variants in Chinese patients with autosomal dominant polycystic kidney disease

“…The methods for identification of PKD genes variants in ADPKD patients were previously described elsewhere. 7 In briefly, the variant analysis of PKD genes were performed with the long-range PCR followed by targeted next-generation sequencing. Sanger sequencing was performed to check the positive variants (please refer to ''the Details in Patients and Methods'').…”

“…The methods for identification of PKD genes variants in ADPKD patients were previously described elsewhere 7 . In briefly, the variant analysis of PKD genes were performed with the long‐range PCR followed by targeted next‐generation sequencing.…”