Alport’s Syndrome

Alport’s syndrome is a hereditary kidney disease, frequently associated with hearing loss and ocular abnormalities. Type IV collagen is the main constituent of the basement membranes. Mutations in the COL4A3, COL4A4 and COL4A5 genes, which encode α3, α4 and α5 chains of type IV collagen, respectively, cause abnormal synthesis of basement membranes including glomerular basement membrane, cochlear and ocular basement membranes. Most families with Alport’s syndrome (85%) have mutations in the COL4A5 gene (X-linked). Mutations affecting COL4A4 and COL4A3 genes cause autosomal recessive, and rarely autosomal dominant Alport’s syndrome. Type of the mutation has significant effect on disease course and prognosis. Kidney failure develops at younger ages in families having nonsense mutations, frame-shift mutations and large deletions in the COL4A5 gene. In families having missense mutations, splice-site mutations or small deletions, kidney failure develops generally at older ages. Mutations in the COL4A3 and COL4A4 genes were identified in some patients with thin basement membrane disease. These patients could be carriers of autosomal recessive Alport’s syndrome. There is no curative treatment for Alport’s syndrome, yet. Gene therapy might be a curative treatment modality in the future.