RT Journal Article
SR Electronic
T1 New COL4A5 mutation in IgA nephropathy
JF Postgraduate Medical Journal
JO Postgrad Med J
FD The Fellowship of Postgraduate Medicine
SP 13
OP 17
DO 10.1136/postgradmedj-2020-138625
VO 98
IS 1155
A1 Xu, Zhenjian
A1 Chen, Junzhe
A1 Yu, Wenjuan
A1 Li, Xiaomei
A1 Lin, Baojuan
A1 Lai, Deyuan
A1 Xu, Anping
A1 Tang, Ying
YR 2022
UL http://pmj.bmj.com/content/98/1155/13.abstract
AB 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.