title: Common ancestry of three Ashkenazi-American families with Alport syndrome and COL4A5 R1677Q.
abstract: Mutations in the basement membrane collagen gene COL4A5 cause the progressive renal glomerular nephropathy and typical hearing loss that occur in X-linked Alport syndrome. Nearly all cases involve distinct mutations, as expected for an X-linked disease that significantly reduces the fitness of affected males. A few exceptional COL4A5 mutations appear to be associated with a reduced disease severity and may account for a significant proportion of late-onset Alport syndrome in populations where a founder effect has occurred. The novel mutation reported here, COL4A5 arg1677gln, has been detected in three independently ascertained Ashkenazi-American families, causes a relatively mild form of nephritis with typical onset in the fourth or fifth decade, and may be involved in the etiology of a large proportion of adult-onset hereditary nephritis in Ashkenazi Jews.
authors.affiliation: Department of Physiology, University of Utah Research Park, Salt Lake City 84108, USA. david.f.barker@m.cc.utah.edu
authors.forename: D F
authors.initials: DF
authors.lastname: Barker
authors.forename: J C
authors.initials: JC
authors.lastname: Denison
authors.forename: C L
authors.initials: CL
authors.lastname: Atkin
authors.forename: M C
authors.initials: MC
authors.lastname: Gregory
mesh_terms: D000328:Adult; D001120:Arginine; D001483:Base Sequence; D003094:Collagen / Q000235:genetics*; D018900:Dinucleotide Repeats; D005060:Europe / Q000208:ethnology; D005190:Family; D005260:Female; D005819:Genetic Markers; D005973:Glutamine; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D009393:Nephritis / Q000235:genetics; D009394:Nephritis, Hereditary / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D018911:Trinucleotide Repeats; D014589:Utah
chemical_list: D005819:Genetic Markers; D005973:Glutamine; D003094:Collagen; D001120:Arginine