Author:
Ding Yin,Tang Xuanli,Du Yuanyuan,Chen Hongyu,Yu Dongrong,Zhu Bin,Yuan Bohan
Abstract
Abstract
Background
Alport syndrome and C3 glomerulonephritis (C3GN) are rare kidney diseases, frequently responsible for familial haematuria, proteinuria, and renal impairment. With the rapid development of molecular genetic testing, Alport syndrome causes have been restricted mostly to variants in the COL4A5 or COL4A3/COL4A4 genes. Moreover, a broad range of genetic contributors in the complement and complement-regulating proteins are definitely implicated in the pathogenesis of C3GN.
Methods
We sought a family with persistent microscopic haematuria associated with renal failure. Clinicopathologic and follow-up data were obtained, and molecular genetic testing was used to screen for pathogenic variants.
Results
We describe a three-generation family with Alport syndrome showing a dominant maternal inheritance. Notably, renal biopsy showed the concurrent histological evidence of C3GN in the proband harbouring an uncommon heterozygous variation in CFHR5, c.508G > A. The alteration leads to replacement of a highly conserved residue at position 170 of the β-strand subunit of CFHR5 (p.Val170Met). In silico analysis showed that the variation was predicted to deregulate complement activation by altering the structural properties and enhancing C3b binding capacity to compete with Complement Factor H (CFH), which was in line with experimental data previously published.
Conclusions
The comorbidity findings between Alport syndrome and C3GN indicate an underlying overlap and require further study.
Funder
Project of Administration of Traditional Chinese Medicine of Zhejiang Province of China
National Natural Science Foundation of China
Project of Science and Technology Agency of Zhejiang Province of China
Publisher
Springer Science and Business Media LLC
Cited by
4 articles.
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