title: Founder effect in GLC1A-linked familial open-angle glaucoma in Northern France.
abstract: Open-angle glaucoma (POAG) is a highly prevalent cause of visual impairment. Six families grouping 71 living patients affected with juvenile-onset and middle-age POAG (age at diagnosis ranging from 10 to 65 years) were linked to the GLC1A locus. All patients carried a mutation of an evolutionarily conserved asparagine residue to a lysine at position 480 (N480K) in the olfactomedin-homology domain, which is encoded by the third exon of the GLC1A gene. The N480K mutation was also identified in 14 unaffected carriers who are at high risk of developing POAG. Although four of the families had ancestors identified in Northern France, the pedigrees could not be interconnected by genealogical investigation. However, haplotype analysis indicated that all the carriers had inherited the N480K mutation from the same founder. Screening of a selected set of 67 POAG patients who originated from Northern France and underwent trabeculectomy before the age of 50, detected one patient with the N480K mutation associated with the same disease haplotype already characterized in the 6 families. This group of 72 POAG patients is the largest one having a GLC1A mutation in common and provides a unique tool to investigate the factors influencing the variable expressivity of the GLC1A gene.
authors.affiliation: INSERM U25, Paris, France.
authors.forename: A P
authors.initials: AP
authors.lastname: Brézin
authors.forename: M F
authors.initials: MF
authors.lastname: Adam
authors.forename: A
authors.initials: A
authors.lastname: Belmouden
authors.forename: M A
authors.initials: MA
authors.lastname: Lureau
authors.forename: A
authors.initials: A
authors.lastname: Chaventré
authors.forename: B
authors.initials: B
authors.lastname: Copin
authors.forename: L
authors.initials: L
authors.lastname: Gomez
authors.forename: S D
authors.initials: SD
authors.lastname: De Dinechin
authors.forename: M
authors.initials: M
authors.lastname: Berkani
authors.forename: F
authors.initials: F
authors.lastname: Valtot
authors.forename: J F
authors.initials: JF
authors.lastname: Rouland
authors.forename: J C
authors.initials: JC
authors.lastname: Dascotte
authors.forename: J F
authors.initials: JF
authors.lastname: Bach
authors.forename: H J
authors.initials: HJ
authors.lastname: Garchon
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D018703:Founder Effect; D005602:France; D005786:Gene Expression Regulation; D008040:Genetic Linkage; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin