Identification of novel and mutations in Korean patients with autosomal dominant polycystic kidney disease

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder. It is caused by mutations in the and genes, and manifests as progressive cyst growth and renal enlargement, resulting in renal failure. Although there have been a few studies on the frequency and spectrum of mutations in and in Korean patients with ADPKD, only exons 36-46, excluding the duplicated region, were analyzed, which makes it difficult to determine accurate mutation frequencies and mutation spectra. Methods: We performed sequence analysis of 20 consecutive unrelated ADPKD patients using long-range polymerase chain reaction (PCR) to avoid pseudogene amplification, followed by exon-specific PCR and sequencing of the all exons of these two genes. Multiplex ligation-dependent probe amplification was performed in patients in whom pathogenic mutations in or were not identified by LR-PCR and direct sequencing to detect large genomic rearrangements. Results: All patients met the diagnostic criteria of ADPKD, and pathogenic mutations were found in 18 patients (90.0%), comprising 15 mutations in and three in . Among 10 novel mutations, eight mutations were found in the gene while two mutations were found in the gene. Eight of 14 mutations (57.1%) were located in the duplicated region. Conclusions: This study expands the spectra of mutations in the and genes and shows that the mutation frequencies of these genes in Korean ADPKD patients are similar to those reported in other ethnicities. Sequence analysis, including analysis of the duplicated region, is essential for molecular diagnosis of ADPKD.