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. 1996 Jun;58(6):1157–1165.

A mutation causing Alport syndrome with tardive hearing loss is common in the western United States.

D F Barker 1, C J Pruchno 1, X Jiang 1, C L Atkin 1, E M Stone 1, J C Denison 1, P R Fain 1, M C Gregory 1
PMCID: PMC1915056  PMID: 8651292

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.

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Selected References

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