3236 Familial adenomatous polyposis: Congenital hypertrophy of the retinal pigment epithelium and distribution of mutations in the adenomatous polyposis coli gene

Purpose : The aim of this study was to localize a gene responsible for Leber’s congenital amaurosis (LCA). an autosomal recessive disease responsible for congenital blindness. It is the most early and severe form of all inherited retinal dystrophies, and umil now the chromosomal localization of the disease-causing gene(s) was unknown. Methods : Thirty-eight affected individuals and fifty-ffve unaffected relatives belonging to 15 multiplex families were ascertained. Among them, five families originated from North-Afdca and ten families originated from various regions in France. For genoty ing, hypervartable microsatellites from the Genethon Data Bank were use 8. Linkage analyses were performed using the MLINK and LINKMAP options of the 5.1 version ol the LINKAGE program. Results : Significant kxf-score values were obtained for markers located on the short arm of chromosome 17 (Zmax = 5.14 at 9 = 0.15 at 01781353 lcous). Homozygosity by descent was observed in four inbred families originated from North-Africa and the MORTON likelihood ratio test gave highly significant results allowing us t(o class our sample in two groups : Group I (North-Africa origin) and Group II (French ori in). In Grou I, me maximum pairwise lad-score was obtained for the D17 8 P 1323 locus ( max = 7.21 at 9= 0.01) while negative results were found in Group II. Conclusion : Here, we report the first mapping ol a gene for LCA to lhe short an of chromosome 17 and provide additional evidence of genetic heterogeneity ol this condition.