Identification of gene mutations in autosomal dominant polycystic kidney disease through targeted resequencing.

نویسندگان

  • Sandro Rossetti
  • Katharina Hopp
  • Robert A Sikkink
  • Jamie L Sundsbak
  • Yean Kit Lee
  • Vickie Kubly
  • Bruce W Eckloff
  • Christopher J Ward
  • Christopher G Winearls
  • Vicente E Torres
  • Peter C Harris
چکیده

Mutations in two large multi-exon genes, PKD1 and PKD2, cause autosomal dominant polycystic kidney disease (ADPKD). The duplication of PKD1 exons 1-32 as six pseudogenes on chromosome 16, the high level of allelic heterogeneity, and the cost of Sanger sequencing complicate mutation analysis, which can aid diagnostics of ADPKD. We developed and validated a strategy to analyze both the PKD1 and PKD2 genes using next-generation sequencing by pooling long-range PCR amplicons and multiplexing bar-coded libraries. We used this approach to characterize a cohort of 230 patients with ADPKD. This process detected definitely and likely pathogenic variants in 115 (63%) of 183 patients with typical ADPKD. In addition, we identified atypical mutations, a gene conversion, and one missed mutation resulting from allele dropout, and we characterized the pattern of deep intronic variation for both genes. In summary, this strategy involving next-generation sequencing is a model for future genetic characterization of large ADPKD populations.

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عنوان ژورنال:
  • Journal of the American Society of Nephrology : JASN

دوره 23 5  شماره 

صفحات  -

تاریخ انتشار 2012