Combination of a Novel Genetic Variant in Gene and a Pathogenic Variant in Gene in a Sibling Renal Disease: A Case Report

Overview

Journal Front Genet

Date 2021 Aug 5

PMID 34349783

Authors

Feng-Mei Wang

Yan Yang

Xiao-Liang Zhang

Yan-Li Wang

Yan Tu

Bi-Cheng Liu

Bin Wang

Affiliations

Soon will be listed here.

Abstract

() variants have been described to play a causative role in auto-immune associated C3 glomerulopathy (C3G) and/or atypical hemolytic uremic syndrome (aHUS) by affecting the dysregulations of alternative pathway activation. However, variant concomitant with variant is scarce. Here, we depict two intriguing cases with concurrent novel heterozygosity for c.2054_2057del (p.Ser687Profs16) variant and a previous reported c.2999G > T (p.Gly1000Val) variant in a pair of siblings. The clinical feature of either paternal variant or maternal variant is just mild microscopic hematuria. Interestingly, their two children with paternal c.2054_2057del (p.Ser687Profs16) variant and maternal c.2999G > T (p.Gly1000Val) variant presented with massive proteinuria, hematuria, and progressive renal failure with poor treatment response. Moreover, complement pathway activation in renal tissue further supports and strengthens the pathogenic role of variant in the development of renal injury in the presence of variant. In conclusion, the rare sibling cases highlight that the extension of genetic analyses in the proband is helpful for the diagnosis and understanding of some family cluster renal diseases.

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