A mutation causing Alport syndrome with tardive hearing loss is common in the western United States. |
| |
Authors: | D. F. Barker C. J. Pruchno X. Jiang C. L. Atkin E. M. Stone J. C. Denison P. R. Fain M. C. Gregory |
| |
Affiliation: | Department of Physiology, University of Utah Health Sciences Center, Salt Lake City, USA. |
| |
Abstract: | Mutations in the COL4A5 gene, located at Xq22, cause Alport syndrome (AS), a nephritis characterized by progressive deterioration of the glomerular basement membrane and usually associated with progressive hearing loss. We have identified a novel mutation, L1649R, present in 9 of 121 independently ascertained families. Affected males shared the same haplotype of eight polymorphic markers tightly linked to COL4A5, indicating common ancestry. Genealogical studies place the birth of this ancestor >200 years ago. The L1649R mutation is a relatively common cause of Alport syndrome in the western United States, in part because of the rapid growth and migratory expansion of mid-nineteenth-century pioneer populations carrying the gene. L1649R affects a highly conserved residue in the NC1 domain, which is involved in key inter- and intramolecular interactions, but results in a relatively mild disease phenotype. Renal failure in an L1649R male typically occurs in the 4th or 5th decade and precedes the onset of significant hearing loss by approximately 10 years. |
| |
Keywords: | |
|
|