AUTOSOMAL RECESSIVE ALPORT SYNDROME - IMMUNOHISTOCHEMICAL STUDY OF TYPE-IV COLLAGEN CHAIN DISTRIBUTION

Alport syndrome (AS) is an hereditary disease of basement membrane col lagen. It is mainly transmitted as a dominant X-linked trait and cause d by mutations in the COL4A5 gene encoding the alpha 5 chain of type I V collagen. However, autosomal recessive AS due to mutations in the CO L4A3 or COL4A4 genes could represent up to 15% of AS. Using the immuno fluorescence technique, we analyzed the distribution of the different chains of type IV collagen in renal (12 specimens) and skin (4 specime ns) basement membranes of 12 AS patients belonging to 11 unrelated kin dreds in which autosomal recessive inheritance had been demonstrated ( 3 kindreds) or was suggested by clinical and genealogic data (8 kindre ds). The renal and skin distribution was normal in one patient with CO L4A4 mutation. A peculiar pattern of distribution of the alpha 3-alpha 5(IV) chains was observed in the other patients. It was characterized the co-absence of the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains in the glomerular basement membrane, and the presence of the alpha 5( IV) chain in a series of extraglomerular basement membranes including capsular, collecting ducts and epidermal basement membranes, a combina tion never observed in X-linked AS. This immunohistochemical pattern i s correlated with the specific distribution of the alpha 3-alpha 5 cha ins of type IV collagen chains within extraglomerular basement membran es. It could be a useful marker for the identification of autosomal re cessive AS.