Major COL4A5 gene rearrangements in patients with juvenile type Alport syndrome
- Telethon Inst. of Genetics and Medicine, Milano (Italy); and others
Mutations in the COL4A5 gene, which encodes the {alpha}5 chain of type IV collagen, are found in a large fraction of patients with X-linked Alport syndrome. The recently discovered COL4A6, tightly linked and highly homologous to COL4A5, represents a second candidate gene for Alport syndrome. We analyzed 177 Italian Alport syndrome families by Southern blotting using cDNA probes from both COL4A5 and COL4A6. Nine unrelated families, accounting for 5% of the cases, were found to have a rearrangement in COL4A5. No rearrangements were found in COL4A6, with the exception of a deletion encompassing the 5{prime} ends of both COL4A5 and COL4A6 genes in a patient with Alport syndrome and leiomyomatosis. COL4A5 rearrangements were all intragenic and included 1 duplication and 7 deletions. Polymerase chain reaction (PCR) analysis was carried out to characterize deletion and duplication boundaries and to predict the resulting protein abnormality. The two smallest deletions involved a single exon (exons 17 and 40, respectively), while the largest ones spanned exons 1 to 36. The clinical phenotype of patients in whom a rearrangement in COL4A5 was detected was severe, with progression to end-stage renal failure in juvenile age and hypoacusis occurring in most cases. These data have some important implications in the diagnosis of patients with Alport syndrome. 34 refs., 3 figs., 1 tab.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 447085
- Journal Information:
- American Journal of Medical Genetics, Vol. 59, Issue 3; Other Information: PBD: 20 Nov 1995
- Country of Publication:
- United States
- Language:
- English
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