*Purpose: Selection of an appropriate donor for kidney transplantation can mitigate the risk of rejection and increase the chances of graft survival. While immunologic matching is prioritized, genetic testing is not often viewed as a critical part of living-related donor selection. Here we describe a case in which all first-degree relatives of a proband were diagnosed with COL4A3-related Alport syndrome after living related kidney donor transplantation.

*Methods: A retrospective case report of clinical and genetic testing findings for a 28-year old living-related kidney transplant recipient and his first-degree relatives.

*Results: The patient first presented to nephrology at age 4 due to hematuria, later leading to a clinical suspicion of Alport Syndrome. Over time, he developed chronic kidney disease (CKD) that progressed to stage 4 (eGFR:16 mL/min/1.73m2) by the age of 23. Following pre-transplantation evaluation, the patient received a kidney from his father. The family history was unremarkable for kidney disease with no known history of proteinuria or impaired kidney function, aside from previous episodes of hematuria in the patient’s brother.

Five years after the transplant, the patient’s brother presented for evaluation of hematuria, prompting further review of this case and genetic testing using a 385 gene panel for kidney diseases (the Renasight^TM test, Natera, Inc.). The patient and his brother were homozygous for the c.2083G>A (p.Gly695Arg) pathogenic missense variant in COL4A3, which disrupts the collagen Gly-X-Y motif and has been reported in multiple cases of Alport syndrome. Each parent was heterozygous for the same COL4A3 variant.

*Conclusions: This case study details the importance of genetic testing prior to kidney transplantation, particularly when considering a living-related donor. The identified variant has been associated with both autosomal dominant and recessive inheritance of Alport syndrome. Additionally, the combination of apparently unaffected parents and different phenotypic presentation between the proband and his sibling indicates reduced penetrance in the heterozygous state and variable expressivity of the variant in the homozygous state. Advanced knowledge of the genetic status of this family could have impacted donor selection especially as the implications of transplantation of a kidney with a heterozygous COL4A3 genotype into an individual with a homozygous genotype is unknown. Further research could also provide insight into factors impacting presentation of COL4A3-related Alport syndrome.

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