DELETIONS OF COLLAGEN TYPE 4 ALPHA 5 GENE IN 4 FAMILIES WITH ALPORT'S SYNDROME

摘要

Alport's syndrome (AS) is manifested by progressive renal disease with typical basement membranes morphology and frequent association wtth ocular signs and deafness. This hereditary disease has been assigned to the collagen type IV alpha 5 gene (COL4A5) located on X chromosome and several mutations have been reported. We present 4 families in which gross deletion of COL4A5 were found as a cause of AS. Using standard Southern blot technique and cDNA probes of COL4A5 absence of restriction fragments or presence of ‘junction” fragments proved a mechanism of the mutation. The span of deletion varied at least from 1.6 to 94 kb. Nonetheless the basic clinical features of the families were indifferent. Deletion of promoter region of COL4A5 In family TR, which might affected another gene, was associated with generalized leiomyomatosis in AS patients - a rare syndromal phenomenon.The wide range of deletion of COL4A5 gene has rather uniform and complete phenotypic manifestation of AS. The correlation between type of a gene rearrangement and clinical picture of AS needs further evaluation. Molecular study of CO4A5 gene and RFLP offers a new tool for genetic counselling.