Hereditary disorders of the glomerular basement membrane

Increased knowledge of the biochemical composition of the glomerular basement membrane (GEM) and the introduction of molecular genetics has shed new light on the hereditary disorders of the GEM. In this review three disorders are highlighted. About 85% of the cases reported as Alport syndrome are transmitted as the X-linked form and are due to mutations of the CO14A5 chain localized at Xq22. The autosomal recessive form can be explained by mutations in the CO14A3 and CO14A4 gene. Anti-GEM nephritis leading to loss of the renal allograft in about 1%-5% of transplanted Alport patients can be the tragic consequence of this disorder. Some patients with familial benign hematuria have an abnormality of CO14A4. The nail-patella syndrome is a rare autosomal dominant disorder defined by the association of nail dysplasia, bone abnormalities, and frequently renal disease. The gene is localized in region 9q34.1, CO15A1 is not involved. The Finnish type is the best known of the different forms of congenital nephrotic syndrome. The gene has been mapped to the long arm of chromosome 19. Diffuse mesangial sclerosis occurs in the isolated form and as part of the Denys Drash syndrome. Disturbances of the WT1 function in the epithelial cells can have a role in the renal abnormalities of the Denys Drash syndrome.