Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a very common hereditary renal disorder. Mutations in PKD1 and PKD2, identified as disease-causing genes, cause about 85% and 15% of ADPKD cases, respectively. Methods: In this study, the mutation analysis of PKD genes was implemented in a Chinese family with suspected ADPKD using targeted clinical exome sequencing (CES). The candidate pathogenic variants were further tested by using Sanger sequencing and validated for co-segregation. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to test abnormal splicing and assess its potential pathogenicity. Results: A novel atypical splicing mutation which belongs to unclassified variants (UCVs), IVS6+5G>C, was identified in three family members by CES and was shown to co-segregate only with the affected individuals. RT-PCR reveals the abnormal splicing of exon 6, thus to cause truncating mutation. These findings suggest that the atypical splice site alteration, IVS6+5G>C, in the PKD2 gene is the potential pathogenic mutation leading to ADPKD in the Chinese family. Conclusion: The data available in this study provided strong evidence that IVS6+5G>C is the potential pathogenic mutation for ADPKD. Meantime, this case also emphasizes the significance of functional analysis of UCVs and genotype-phenotype correlation in ADPKD.
A new atypical splice mutation of PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese family
