A novel missense mutation of COL4A5 gene alter collagen IV α5 chain to cause X-linked Alport syndrome in a Chinese family

Background: X-linked Alport syndrome (XLAS) is the most common form of Alport syndrome (AS), involves mutations in the COL4A5 gene encoding the type IV collagen alpha 5 chain. In this research, we will report the analysis of the COL4A5 gene in a Chinese family with XLAS, and investigate the effect of the missense mutation of this family on type IV collagen. Methods: Targeted sequencing using next-generation sequencing (NGS) was conducted for genes (COL4A3/4/5). Normal and mutation COL4A5 plasmids were constructed and then transfected into human podocytes, none plasmid and empty plasmid transfection as control. And then real-time PCR, western blot and indirect immunofluorescence were used to detect the COL4A1/3/5 mRNA, protein, and immunofluorescence expression of each group. Results: In this study, we found an Alport family, and the whole exon sequencing found a new missense mutation c.1844G>C in exon 25. The results of real-time PCR, western blot and immunofluorescence showed that in the mutation group, both the mRNA and protein levels of COL4A5 were significantly reduced. Conclusions: c.1844G>C is a functional variation of COL4A5, which might play a very important role in the occurrence and development of AS.