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A large kindred with adult-type X-linked Alport syndrome was studied with regard to a defect in the recently described COL4A5 collagen gene. Southern blot analysis with COL4A5 cDNA probes showed loss of a MspI restriction site. Direct sequencing of cDNA amplified from lymphoblast mRNA demonstrated a single-base substitution converting a glycine codon to arginine at position 325 in the alpha 5 chain of type IV collagen. The triple-helical collagenous domain of alpha 5(IV), characterized by a Gly-X-Y repeat sequence, is interrupted 22 times by noncollagenous sequences. The mutation creates an additional interruption in the Gly-X-Y repeat motif, between interruptions 4 and 5. It is interesting that such glycine substitutions inside the COL1A1 or COL1A2 genes have been associated with many cases of osteogenesis imperfecta. This gly325-to-arg substitution presumably alters the triple-helix formation, and, in turn, modifies the ultrastructural and functional characteristics of the type IV collagen network inside the glomerular basement membrane.

The expression of HLA, human and mouse beta2-microglobulin (beta2m), P red blood cell antigen and a receptor for marmoset red blood cells (MaRBC) were studied on 18 man/mouse and man/Chinese hamster hybrids. A positive correlation was found between the expression of HLA, P, and the receptor for MaRBC, which we interpret as a possible synteny between these different loci. We studied 3 hybrid clones where HLA antigens are still expressed despite the absence of human beta2m and where redistribution experiments demonstrate that HLA is associated with mouse beta2m. Synteny between HLA and the receptor for MaRBC can be a useful tool to select HLA-positive hybrid clones.