Mapping and mutation screening of two different loci for primary congenital glaucoma (buphthalmos)

Purpose: To identify the chromosomal location of Primary Congenital Glaucoma (Buphthalmos) and to screen regional candidate genes for mutation. Methods: We used a combination of candidate regional and general positional mapping strategy to identify the chromosomal locations of this condition. Results: Genetic linkage study of 20 families positioned the first locus (GLC3A) to 2p21 (Genomics, 1995; 30:171-177) and a second locus (GLC3B) to 1 p36 (Hum. Mole. Genet. 1996; 5(8): 1199-1203). Twelve families showed no recombination with a group of 17 tightly linked DNA markers from the 2p21 region. Inspection of haplotypes in 7 consanguineous families indicated that the disease gene lies within a region of about 2.5 cM that is flanked by D2S1325 and D2S1356. The remaining 8 families did not exhibit any linkage to this region of chromosome 2. Further screening of the genome revealed no recombination in 4 families with two tightly linked markers of D1S402 and DIS2834 located on Ip36 region. The GLC3B locus in these families is confined within a 3 cM interval that is flanked by D1S228 and D1S507. There remained 4 other families that are not linked to the two identified regions. Screening of a new multi-generational consanguineous family also proved no linkage to the two locations of 2p21 and Ip36. Conclusions: At least three different loci are responsible for primary congenital glaucoma.