Integration of Genetic Testing and Pathology for the Diagnosis of Adults with FSGS
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. Whole-exome sequencing was performed in adults with FSGS diagnosed between 197...
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Published in | Clinical journal of the American Society of Nephrology Vol. 14; no. 2; pp. 213 - 223 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society of Nephrology
07.02.2019
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Subjects | |
Online Access | Get full text |
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Summary: | 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.
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.
The cohort was composed of 193 individuals from 179 families. Nearly half (49%) developed ESKD at a mean age of 47±17 years. The genetic diagnostic rate was 11%. Of definitely pathogenic variants, 55% were in
(
), 40% were in podocyte genes, and 5% were in CAKUT genes. Many, but not all individuals with
definitely pathogenic variants had some evidence of glomerular basement membrane abnormalities. The estimated mean survival/age of kidney failure for individuals with
definitely pathogenic variants was 58 years (95% confidence interval, 49 to 69), far later than what has been reported in the literature. Likely pathogenic variants were identified in an additional 9% of the cohort, with most in
. Correlation with glomerular basement membrane morphology suggested a causal role for at least some of these likely pathogenic variants.
Even with an expanded gene panel, we find that
disorders are the leading monogenic cause in adults diagnosed with FSGS.
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_01_15_CJASNPodcast_19_02_.mp3. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1555-9041 1555-905X |
DOI: | 10.2215/CJN.08750718 |