AUTHOR=Wang Feng-mei , Yang Yan , Zhang Xiao-liang , Wang Yan-li , Tu Yan , Liu Bi-Cheng , Wang Bin 

TITLE=Combination of a Novel Genetic Variant in CFB Gene and a Pathogenic Variant in COL4A5 Gene in a Sibling Renal Disease: A Case Report

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.690952

DOI=10.3389/fgene.2021.690952

ISSN=1664-8021

ABSTRACT=<p><italic>Complement factor B</italic> (<italic>CFB</italic>) 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, <italic>CFB</italic> variant concomitant with <italic>COL4A5</italic> variant is scarce. Here, we depict two intriguing cases with concurrent novel heterozygosity for <italic>CFB</italic> c.2054_2057del (p.Ser687Profs<sup>∗</sup>16) variant and a previous reported <italic>COL4A5</italic> c.2999G &gt; T (p.Gly1000Val) variant in a pair of siblings. The clinical feature of either paternal <italic>CFB</italic> variant or maternal <italic>COL4A5</italic> variant is just mild microscopic hematuria. Interestingly, their two children with paternal <italic>CFB</italic> c.2054_2057del (p.Ser687Profs<sup>∗</sup>16) variant and maternal <italic>COL4A5</italic> c.2999G &gt; 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 <italic>CFB</italic> variant in the development of renal injury in the presence of <italic>COL4A5</italic> 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.</p>