Journal article
Screening of Living Kidney Donors for Genetic Diseases Using a Comprehensive Genetic Testing Strategy
American journal of transplantation, Vol.17(2), pp.401-410
02/2017
DOI: 10.1111/ajt.13970
PMCID: PMC5297870
PMID: 27434427
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.
Details
- Title: Subtitle
- Screening of Living Kidney Donors for Genetic Diseases Using a Comprehensive Genetic Testing Strategy
- Creators
- C P Thomas - VA Medical Center, Iowa City, IAM A Mansilla - Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IAR Sompallae - Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IAS O Mason - Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IAC J Nishimura - Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IAM J Kimble - Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IAC A Campbell - Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IAA E Kwitek - Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IAB W Darbro - The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IAZ A Stewart - Department of Surgery, Division of Transplant Surgery, Carver College of Medicine, University of Iowa, Iowa City, IAR J H Smith - Department of Otorhinolaryngology, Carver College of Medicine, University of Iowa, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- American journal of transplantation, Vol.17(2), pp.401-410
- DOI
- 10.1111/ajt.13970
- PMID
- 27434427
- PMCID
- PMC5297870
- NLM abbreviation
- Am J Transplant
- ISSN
- 1600-6143
- eISSN
- 1600-6143
- Publisher
- United States
- Language
- English
- Date published
- 02/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Medical Genetics and Genomics; Obstetrics and Gynecology; Otolaryngology; Internal Medicine; Iowa Institute of Human Genetics
- Record Identifier
- 9983986083402771
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