Do mutations in COL4A1 or COL4A2 cause thin basement membrane nephropathy (TBMN)?

Ke Zhang, Stephen Tonna, Yan Yan Wang, Kesha Rana, Smitha Padavarat, Judy Savige

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)


Thin basement membrane nephropathy (TBMN) is the commonest cause of persistent glomerular haematuria and often presents in childhood. Only 40 of affected individuals have mutations identified in the COL4A3 and COL4A4 genes, but mutations in the genes for other COL4A isoforms also result in thinned membranes in humans (COL4A5) and mice (COL4A1). This study examined whether COL4A1/COL4A2 represented a further genetic locus for TBMN. Nine families with TBMN in whom haematuria did not segregate with COL4A3/COL4A4, were examined for linkage to COL4A1/COL4A2 using five micro-satellite markers. In addition, index cases from these families plus a further 14 unrelated individuals with TBMN that was not due to COL4A3 or COL4A4 mutations (n=23) were screened for mutations in each of the 52 exons of COL4A1 and the 47 exons of COL4A2 using single stranded conformational analysis (SSCA). DNA samples that demonstrated bandshifts were sequenced. Haplotype analysis demonstrated that haematuria segregated with the COL4A1/COL4A2 locus in only two small families (2/9, 22 ). No definite COL4A1 or COL4A2 mutations were identified in the 23 unrelated individuals with TBMN although novel polymorphisms were demonstrated. This study indicates that COL4A1/COL4A2 does not represent a further major genetic locus for TBMN.
Original languageEnglish
Pages (from-to)645 - 651
Number of pages7
JournalPediatric Nephrology
Issue number5
Publication statusPublished - 2007
Externally publishedYes

Cite this

Zhang, K., Tonna, S., Wang, Y. Y., Rana, K., Padavarat, S., & Savige, J. (2007). Do mutations in COL4A1 or COL4A2 cause thin basement membrane nephropathy (TBMN)? Pediatric Nephrology, 22(5), 645 - 651.