Integration of Genetic Testing and Pathology for the Diagnosis of Adults with FSGS

BACKGROUND AND OBJECTIVES: FSGS and nephrotic syndrome studies have shown that single gene causes are more likely to be found in pediatric cases than adults. Consequently, many studies have examined limited gene panels in largely pediatric cohorts. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Whole-exome sequencing was performed in adults with FSGS diagnosed between 1976 and 2017 in the Toronto GN Registry. An expanded panel of 109 genes linked to FSGS, glomerular basement membrane abnormalities, as well as causes of pediatric ESKD including congenital abnormalities of the kidney and urinary tract (CAKUT) and nephronophthisis, were examined. Correlation with glomerular basement membrane morphology suggested a causal role for at least some of these likely pathogenic variants. CONCLUSIONS: disorders are the leading monogenic cause in adults diagnosed with FSGS. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_01_15_CJASNPodcast_19_02_.mp3.