Screening of living kidney donors for genetic diseases using a comprehensive gen

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http://onlinelibrary.wiley.com/doi/10.1111/ajt.13970/abstract

Screening of living kidney donors for genetic diseases using a comprehensive genetic testing strategy
      C P Thomas,
 M A Mansilla,
 R Sompallae,
 S O Mason,
 C J Nishimura,
 M J Kimble,
 C A Campbell,
 A E Kwitek,
 B W Darbro,
 Z A Stewart,
 R J H Smith
 
      Accepted manuscript online: 19 July 2016
      DOI: 10.1111/ajt.13970

AJT
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Abstract
Related living kidney donors (LKDs) are at higher risk of end-stage renal disease (ESRD) compared to unrelated LKDs. A genetic panel was developed to screen 115 genes associated with renal diseases. We used this panel to screen 6 negative controls, 4 transplant candidates with presumed genetic renal disease, and 6 related LKDs. After removing common variants, pathogenicity was predicted using six algorithms to score genetic variants based on conservation and function. All variants were evaluated in the context of patient phenotype and clinical data. We identified causal variants in 3 of the 4 transplant candidates. Two patients with a family history of autosomal dominant polycystic kidney disease segregated variants in PKD1. These findings excluded genetic risk in 3 of 4 relatives accepted as potential LKDs. A third patient with an atypical history for Alport syndrome had a splice site mutation in COL4A5. This pathogenic variant was excluded in a sibling accepted as a LKD. In another patient with a strong family history of ESRD, a negative genetic screen combined with negative comparative genomic hybridization in the recipient facilitated counseling of the related donor. This genetic renal disease panel will allow rapid, efficient and cost-effective evaluation of related LKDs.