Initial experience from a renal genetics clinic demonstrates a distinct role in patient management

Abstract

Purpose: A Renal Genetics Clinic (RGC) was established to optimize diagnostic testing, facilitate genetic counseling, and direct clinical management.

Methods: Retrospective review of patients seen over a two-year period in the RGC.

Results: One hundred eleven patients (mean age: 39.9 years) were referred to the RGC: 65 for genetic evaluation, 19 for management of a known genetic disease, and 18 healthy living kidney donors (LKDs) and their 9 related transplant candidates for screening. Forty-three patients underwent genetic testing with a diagnosis in 60% of patients including 9 with Alport syndrome, 7 with autosomal dominant polycystic kidney disease (ADPKD), 2 with genetic focal segmental glomerulosclerosis (FSGS), 2 with PAX2-mediated CAKUT, and 1 each with autosomal recessive polycystic kidney disease (ARPKD), Dent, Frasier, Gordon, Gitelman, and Zellweger syndromes. Four of 18 LKDs were referred only for APOL1 screening. For the remaining 14 LKDs, their transplant candidates were first tested to establish a genetic diagnosis. Five LKDs tested negative for the familial genetic variant, four were positive for their familial variant. In five transplant candidates, a genetic variant could not be identified.

Conclusion: An RGC that includes genetic counseling enhances care of renal patients by improving diagnosis, directing management, affording presymptomatic family focused genetic counseling, and assisting patients and LKDs to make informed decisions.

Keywords: comprehensive renal panel; genetic counseling; genetic screening; next-generation sequencing; presymptomatic testing.

Fig. 1. Outcome of genetic clinic visit in 65 patients referred for genetic evaluation.

See Table 1. Forty-three patients were tested and of those tested, 58% had a genetic diagnosis established (tested positive). Actual numbers and percentages (in parentheses) for each category are shown. Three patients had one pathogenic variant for an autosomal recessive disorder (heterozygous carrier) that fit the phenotype. In seven patients, the preliminary evaluation concluded that genetic testing would not be informative (testing considered unnecessary).

Fig. 2. Pedigree chart for subjects 29–1, 29–2, and 29–3.

The identified heterozygous genetic variant COL4A3 p.Gly934Arg (G934R) was initially classified as a variant of unknown significance (VUS) (American College of Medical Genetics and Genomics [ACMG] criteria: PM1, PM2, PP3) but following segregation analysis was reclassified as likely pathogenic (ACMG: PM1, PM2, PP1, PP3). CKD chronic kidney disease, GFR glomerular filtration rate.