Co-existence of Alport syndrome and C3 glomerulonephritis in a proband with family history

被引:5
作者
Ding, Yin [1 ]
Tang, Xuanli [1 ]
Du, Yuanyuan [1 ]
Chen, Hongyu [1 ]
Yu, Dongrong [1 ]
Zhu, Bin [1 ]
Yuan, Bohan [1 ]
机构
[1] Zhejiang Chinese Med Univ, Key Lab Management Kidney Dis Zhejiang Prov, Dept Nephrol, Hangzhou TCM Hosp, Tiyuchang Rd 453, Hangzhou 310007, Peoples R China
基金
中国国家自然科学基金;
关键词
Rare renal disease; Alport syndrome; C3GN; CFHR5; p; Val170Met; H-RELATED PROTEIN-5; VARIANTS; GENE; IDENTIFICATION; GLOMERULOPATHY; MUTATIONS; ABNORMALITIES; GUIDELINES; INSIGHTS;
D O I
10.1186/s40001-021-00543-5
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 beta-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.
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页数:9
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