A DELETION MUTATION IN THE 3' END OF THE ALPHA-5(IV) COLLAGEN GENE INJUVENILE-ONSET ALPORT SYNDROME

Alport syndrome is a hereditary progressive glomerular basement membra ne disorder in which juvenile-or adult-onset renal failure is often ac companied by sensorineural deafness and ocular abnormalities. Recently , mutations have been found in the type IV collagen alpha 5 chain gene in patients with X-linked Alport syndrome. This study searched for ge ne mutations in seven unrelated Japanese patients by the use of conven tional Southern blot analysis with cDNA probes for the carboxyl-termin al noncollagenous domain that is encoded by exons 46 to 51. A deletion mutation was found in a patient who developed juvenile-onset (age 15) ESRD with typical ultrastructural glomerular basement membrane destru ction and sensorineural hearing loss but no characteristic ocular abno rmalities. His mother showed hematuria and proteinuria with nomal rena l function, suggesting that she may be the heterozygous carrier. Exon- specific polymerase chain reaction amplified the coding sequence of ex on 48 but not exons 49 to 51. Analysis with pulsed-field gel electroph oresis revealed that the deletion is approximately 10 kb in length and does not involve the CpG island, which is located in the 3' distal si te of the gene. Identification of this novel deletion causing juvenile -type Alport syndrome would contribute to elucidating the mechanisms o f renal failure progression in the syndrome.