Identification of novel PKD1 and PKD2 mutations in Korean patients with autosomal dominant polycystic kidney disease

BMC Medical Genetics

Curie Ahn³  Young-Hwan Hwang¹  Chang-Seok Ki²  Jong-Won Kim²  Myoung-Gun Lee²  Kyunghoon Lee²  Hayne Cho Park³  Rihwa Choi² 

[1] Department of Internal Medicine, Eulji General Hospital, (139-872), 1306 Dunsan 2(i)-dong, Seo-gu, Daejeon, Seoul, South Korea;Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, (135-710) 81 Irwon-Ro Gangnam-gu, Seoul, South Korea;Department of Internal Medicine, Seoul National University College of Medicine, (110-744) 28 Yeongeon-dong, Jongno-gu, Seoul, South Korea

关键词: PKD2;    PKD1;    Mutation;    Korean;    Autosomal dominant polycystic kidney disease;   

Others  :  1090120
DOI  :  10.1186/s12881-014-0129-y

 received in 2014-07-10, accepted in 2014-11-20,  发布年份 2014

【 摘 要 】

Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder. It is caused by mutations in the PKD1 and PKD2 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 PKD1 and PKD2 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 PKD1 or PKD2 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 PKD1 and three in PKD2. Among 10 novel mutations, eight mutations were found in the PKD1 gene while two mutations were found in the PKD2 gene. Eight of 14 PKD1 mutations (57.1%) were located in the duplicated region.

Conclusions

This study expands the spectra of mutations in the PKD1 and PKD2 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.

【 授权许可】

   
2014 Choi et al.; licensee BioMed Central Ltd.

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