Purpose IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis and a leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Recently, some case reports have shown that COL4A5 mutation is associated with IgAN. Here, we identified a new COL4A5 gene mutation in IgAN in a Chinese family.
Materials and Methods In the present study, the proband and his 23-year-old younger brother were both diagnosed with IgAN, manifested as haematuria, proteinuria and chronic kidney injury without hearing loss or ocular symptoms. Additionally, the proband’s 30-year-old younger brother, also diagnosed with ESKD, had been undergoing dialysis for 2 years with normal hearing and eyesight. To exclude genetic disease, we conducted whole-exome sequencing and Sanger sequencing assays.
Results We found a new mutation in the COL4A5 gene (chrX:107 814 698, c.438+2->AAACCAATTATA-), a novel insertion mutation. Using vector transcription and Minigene transcriptional analyses, we verified, for the first time, the novel mutation pathogenicity of the COL4A5 gene.
Conclusion Together with other published data, we suggest that genetic screening should be performed in IgAN, particularly for patients with a familial history. The effects of different mutated splice sites of the COL4A5 gene, as well as the tissue specificity of the splicing machinery contributing to the pathogenesis and prognosis of IgAN, remains unclear and warrants further exploration in the future.
- Chronic renal failure
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ZX and JC contributed equally
Contributors AX and YT conceived and designed the study. ZX and JC acquired the data and drafted the manuscript. All the authors contributed to the writing of the manuscript. WY, XL, BL and DL performed the statistical analysis.
Funding This work was supported in part by grants from the National Natural Science Foundation of China (General Program: 81870481), Sun Yat-Sen Clinical Research Cultivating Program (SYS-C-201905) and Medical Scientific Research Foundation of Guangdong Province of China (A2020431).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study followed the tenets of the Declaration of Helsinki and was approved by the institutional review board of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available in a public, open access repository.