Purpose: To study the clinical features and to perform genetic linkage study in two large Chinese families with autosomal dominant juvenile-onset primary open-angle glaucoma (POAG).
Methods: Eighteen members of one Chinese family and 25 members of a second Chinese family with juvenile-onset primary open-angle glaucoma (POAG) were investigated. Thirteen members in one family and 14 members in the second family were diagnosed with juvenile-onset POAG. A genome-wide linkage scan was performed on one family using 411 short tandem repeat (STR) markers. Subsequent fine mapping was performed in the two study families using a modified fluorescent labeled M13 primer method.
Results: A whole genome-wide scan in one family showed linkage to chromosome 2p15-p16 with a two-point maximum LOD score of 5.01 at theta=0 between the disease phenotype and STR marker D2S337. The second family was also mapped to the same locus with a two-point maximum LOD score of 6.30 at theta=0 for D2S378. Haplotype analysis in these two families demonstrated that they shared the same disease haplotype, suggesting they have inherited the mutation from a common founder. The maximum LOD scores were 8.93 at theta=0 for D2S378 and 9.9 at theta=0 for D2S337 when the two families were combined for analysis. The disease interval for these two families was localized to 9.2 cM or 13.3 Mb between D2S123 and D2S2397. There are 42 known genes/transcripts within the interval. Five of these genes were sequenced, and no disease-causing mutation was identified in either family.
Conclusions: This novel juvenile-onset POAG locus on chromosome 2p15-16 is overlapped by the Glaucoma 1, open angle, H (GLC1H) locus for adult-onset POAG. Eventual identification of the disease-causing gene will provide insights into the pathogenesis of POAG.