New COL4A5 mutation in IgA nephropathy.

Abstract

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 <i>COL4A5</i> mutation is associated with IgAN. Here, we identified a new <i>COL4A5</i> gene mutation in IgAN in a Chinese family. 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. We found a new mutation in the <i>COL4A5</i> 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 <i>COL4A5</i> gene. 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 <i>COL4A5</i> 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.