Relationship between COL4A5 gene mutation and distribution of type IV collagen in male X-linked Alport syndrome

Abstract

The renal immunohistochemical distribution of collagen IV chains was studied with a monoclonal antibody series recognizing the α1(IV) to αb(IV) chains in nine males with X-linked Alport syndrome whose COL4A5 mutation had been already identified. Two patients had a deletional mutation, six patients had a missense and one patient had a splicing site mutation. The 3/4 (IV) to α6(IV) chains were completely absent in the renal basement membrane of the two patients with a deletional mutation. On the contrary, in four of six patients with a missense mutation (substitution of a glycine within collagenous domain), antigenicity of the α3(IV) to α5(IV) chains was recognized in the glomerular basement membrane although it was weak. In addition, one of the remaining patients showed a normal histochemical pattern of all type IV collagen chains, while the rest one showed completely absent of the 3/4 (IV) to α5(IV) chains at the same pattern of deletional mutation. One patient with a splice site mutation showed complete absence of the α3(IV) to α5(IV) chains from the glomerular basement membrane, but weak staining of the ≱(IV) and α6(IV) chains from the Bowman's capsular basement membrane. Our observations indicated that there is a variety in the staining of the α3(IV) to ↑(IV) antibodies among male patients with COL4A5 mutations.