RELATIONSHIP BETWEEN COL4A5 GENE MUTATION AND DISTRIBUTION OF TYPE-IVCOLLAGEN IN MALE X-LINKED ALPORT SYNDROME

The renal immunohistochemical distribution of collagen IV chains was s tudied with a monoclonal antibody series recognizing the alpha 1(IV) t o alpha 6(IV) chains in nine males with X-linked Alport syndrome whose COL4A5 mutation had been already identified. Two patients had a delet ional mutation, six patients had a missense mutation and one patient h ad a splicing site mutation. The alpha 3(IV) to alpha 6(IV) chains wer e 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), antigenecity of the alpha 3(IV) to alpha 5(IV) chains was re cognized 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 comp letely absent of the alpha 3(IV) to alpha 5(IV) chains at the same pat tern of deletional mutation. One patient with a splice site mutation s howed complete absence of the alpha 3(IV) to alpha 5(IV) chains from t he glomerular basement membrane, but weak staining of the alpha 5(IV) and alpha 6(IV) chains from the Bowman's capsular basement membrane. O ur observations indicated that there is variety in the staining of the alpha 3(IV) to alpha 6(IV) antibodies among male patients with COL4A5 mutations.