Identification of mutations in the α3(IV) and α4(IV) collagen genes in autosomal recessive Alport syndrome

Abstract

Alport syndrome (AS) is an hereditary disease of basement membranes characterized by progressive renal failure and deafness. Changes in the glomerular basement membrane (GBM) in AS suggest that the type IV collagen matrix, the major structural component of GBM, is disrupted. We recently isolated the genes for two type IV collagens, α3(IV) and α4(IV), that are encoded head-to-head on human chromosome 2. These chains are abundant in normal GBM but are sometimes absent in AS. We screened for mutations in families in which consanguinity suggested autosomal recessive inheritance. Homozygous mutations were found in α3(IV) in two families and in α4(IV) in two others, demonstrating that these chains are important in the structural integrity of the GBM and that there is an autosomal form of AS in addition to the previously-defined X-linked form.