Faculty Collaboration Database

Screening of Living Kidney Donors for Genetic Diseases Using a Comprehensive Genetic Testing Strategy. Am J Transplant 2017 Feb;17(2):401-410

Date

07/20/2016

Pubmed ID

27434427

Pubmed Central ID

PMC5297870

DOI

10.1111/ajt.13970

Scopus ID

2-s2.0-84983386859 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

Related living kidney donors (LKDs) are at higher risk of end-stage renal disease (ESRD) compared with unrelated LKDs. A genetic panel was developed to screen 115 genes associated with renal diseases. We used this panel to screen six negative controls, four transplant candidates with presumed genetic renal disease and six 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 three of the four transplant candidates. Two patients with a family history of autosomal dominant polycystic kidney disease segregated variants in PKD1. These findings excluded genetic risk in three of four 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 an 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.

Author List

Thomas CP, Mansilla MA, Sompallae R, Mason SO, Nishimura CJ, Kimble MJ, Campbell CA, Kwitek AE, Darbro BW, Stewart ZA, Smith RJ

Author

Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Female
Genetic Markers
Genetic Testing
Glomerulosclerosis, Focal Segmental
High-Throughput Nucleotide Sequencing
Humans
Kidney Transplantation
Living Donors
Male
Mass Screening
Middle Aged
Mutation
Pedigree
Polycystic Kidney, Autosomal Dominant
Renal Insufficiency, Chronic
Young Adult