Different mutations in the COL4A5 collagen gene in two patients with different features of Alport syndrome

Alport syndrome is a hereditary renal disease in which progressive renal failure is often accompanied by sensorineural deafness and ocular abnormalities. Recently, mutations were detected in the type IV collagen alpha 5 chain gene in Alport syndrome patients. We searched for mutations in this gene in 18 unrelated patients, and in two patients abnormalities were detected. In the gene of patient BB we identified a complex deletion, which included the exons encoding the non-collagenous domain and part of the collagenous region. This patient showed early onset nephritis (end-stage renal disease at 17 years) with deafness. Within a year after receiving a kidney from an unrelated donor, he developed an antiglomerular basement membrane nephritis. In patient WJ a point-mutation was detected, changing a tryptophane into a serine in the non-collagenous domain. His clinical features are milder (renal failure at 33 years, no hearing loss), and a recent renal allograft did not provoke antiglomerular basement membrane disease. These initial data suggest that differences in the extent of disruption of the non-collagenous domain may correlate with the severity and/or heterogeneity of Alport syndrome and with the development of nephritis in renal allografts.