THE CLINICAL SPECTRUM OF TYPE-IV COLLAGEN MUTATIONS

Clinical manifestations of type IV collagen mutations can vary from th e severe, clinically and genetically heterogeneous renal disorder, Alp ort syndrome, to autosomal dominant familial benign hematuria. The pre dominant form of Alport syndrome is X-linked; more than 160 different mutations have yet been identified in the type IV collagen alpha 5 cha in (COL4A5) gene, located at Xq22-24 head to head to the COL4A6 gene. The autosomal recessive form of Alport syndrome is caused by mutations in the COL4A3 and COL4A4 genes, located at 2q35-37, Recently, the fir st mutation in the COL4A4 gene was identified in familial benign hemat uria. This paper presents an overview of type IV collagen mutations, i ncluding eight never COL4A5 mutations from our own group in patients w ith Alport syndrome. The spectrum of mutations is broad and provides i nsight into the clinical heterogeneity of Alport syndrome with respect to age at renal failure and accompanying features such as dearness, l eiomyomatosis, and anti-GBM nephritis. (C) 1991 Wiley-Liss, Inc.