FOUNDER EFFECT IN GLC1A-LINKED FAMILIAL OPEN-ANGLE GLAUCOMA IN NORTHERN FRANCE

Open-angle glaucoma (POAG) is a highly prevalent cause of visual impai rment, Six families grouping 71 living patients affected with juvenile -onset and middle-age POAG (age at diagnosis ranging from 10 to 65 yea rs) were linked to the GLC1A locus, All patients carried a mutation of an evolution arily conserved asparagine residue to a lysine at positi on 480 (N480K) in the olfacto-medin-homology domain, which is encoded by the third exon of the GLC1A gene, The N480K mutation was also ident ified in 14 unaffected carriers who are at high risk of developing POA G. Although four of the families had ancestors identified in Northern France, the pedigrees could not be interconnected by genealogical inve stigation, 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 patie nt with the N480K mutation associated with the same disease haplotype already characterized in the 6 families, This group of 72 POAG; patien ts is the largest one having a GLC1A mutation in common and provides a unique tool to investigate the factors influencing the variable expre ssivity of the GLC1A gene. (C) 1998 Wiley-Liss, Inc.