A mutation causing Alport syndrome with tardive hearing loss is common in the western United States.
A mutation causing Alport syndrome with tardive hearing loss is common in the western United States.
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DOI：
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发表时间：
1996-06
影响因子：
9.8
通讯作者：
D. Barker;C. Pruchno;X. Jiang;C. Atkin;E. Stone;J. Denison;P. Fain;M. Gregory
中科院分区：
文献类型：
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作者：
D. Barker;C. Pruchno;X. Jiang;C. Atkin;E. Stone;J. Denison;P. Fain;M. Gregory
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.
