• Zhenjian Xu, Junzhe Chen, Wenjuan Yu, Xiaomei Li, Baojuan Lin, Deyuan Lai, Anping Xu, and Ying Tang.
• Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
• Postgrad Med J. 2022 Jan 1; 98 (1155): 13-17.

PurposeIgA 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 MethodsIn 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.ResultsWe 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.ConclusionTogether 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.© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

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