Background & objective: The alpha4 chain of the type 4 collagen family is an important component of the glomerular basement membrane (GBM) in the kidney. It is encoded by the COL4A4 gene, and mutations of this gene are known to be associated with thin basement membrane nephropathy (TBMN). To better understand the contribution of variants in the COL4A4 gene to TBMN, we investigated the sequence of the complete COL4A4 gene in 45 Korean patients with TBMN.
Methods: Genomic DNA was obtained from the peripheral blood lymphocytes. For the analysis of the COL4A4 gene, all the exons including splicing sites were amplified by PCR and screened by direct sequencing analysis.
Results: Eight novel COL4A4 sequence variants were found in these patients. Two of these variants, G199R and G1606E, were possibly pathogenic variants affecting the phenotype. None of these variants were observed in 286 chromosomes from normal Korean control subjects. In addition, 39 polymorphisms including 7 novel SNPs were identified in this study.
Interpretation & conclusion: The frequency of COL4A4 mutations in Korean patients with TBMN is low and the other cases may have mutations in other genes like COL4A3. Screening of the COL4A3 gene and finding a novel causative gene for TBMN will help clarify the pathogenesis of this disorder and perhaps for distinguishing TBMN from Alport syndrome.