The 2014International Workshop on Alport Syndrome

Abstract

Alport syndrome, historically referred to as hereditary glomerulonephritis with sensorineural deafness and anterior lenticonus, is a genetic disease of collagen α3α4α5(IV) resulting in renal failure. The collagen α3α4α5(IV) heterotrimer forms a network that is a major component of the kidney glomerular basement membrane (GBM) and basement membranes in the cochlea and eye. Alport syndrome, estimated to affect 1 in 5000-10,000 individuals, is caused by mutations in any one of the three genes that encode the α chain components of the collagen α3α4α5(IV) heterotrimer: COL4A3, COL4A4, and COL4A5. Although angiotensin-converting enzyme inhibition is effective in Alport syndrome patients for slowing progression to end-stage renal disease, it is neither a cure nor an adequate long-term protector. The 2014 International Workshop on Alport Syndrome, held in Oxford, UK, from January 3-5, was organized by individuals and families living with Alport syndrome, in concert with international experts in the clinical, genetic, and basic science aspects of the disease. Stakeholders from diverse communities-patient families, physicians, geneticists, researchers, Pharma, and funding organizations-were brought together so that they could meet and learn from each other and establish strategies and collaborations for the future, with the overall aim of discovering much needed new treatments to prolong kidney function.

Figure 1

The normal human kidney glomerular basement membrane (GBM) contains primarily collagen α3α4α5(IV), which is defective or missing in Alport syndrome. A frozen human kidney section was stained in red for COL4A4, representing the α3α4α5(IV) network, and in green for collagen α1α1α2(IV). The GBM and a few tubular basement membranes are enriched in collagen α3α4α5(IV). The α1α1α2(IV) network is detected primarily in the mesangial matrix and in tubular basement membranes.