Genetics of middle-age onset primary open angle glaucoma

Purpose: To determine whether an adult-onset variety of primary open-angle glaucoma in family UM:POAG1 is linked to the previously mapped GLC1A juvenile-onset primary open-angle glaucoma locus on chromosome 1q or whether linkage can be excluded. Metnods: Microsatellite repeat markers from the 9 cM D1S196 to D1S218 interval containing the GLC1A gene were amplified by polymerase chain reaction from DNA samples collected from eleven members of one sibship in family UM:POAG1. Haplotype analysis was carried out, including calculation of the probability the observed data would have been obtained if the underlying cause of primary open-angle glaucoma in this family were a defect in a gene located in the tested interval. Linkage analysis was carried out under an autosomal dominant model for GLC1A glaucoma. Results: In family UM:POAG1, six surviving and one deceased member of a sibship of 13 individuals were diagnosed with primary open-angle glaucoma during the fifth and sixth decade of life. POAG1 glaucoma has a later average age at diagnosis and significantly less elevation in intraocular pressure than GLC1A glaucoma so far described. Haplotype analysis shows that it is unlikely that the reported data would have been observed if primary open angle glaucoma in this pedigree were due to the GLC1A locus on chromosome 1q21-q31. Linkage analysis under the juvenile glaucoma autosomal dominant model allowed exclusion of linkage across the entire GLC1A genetic inclusion interval, with a maximum lod score in the interval of -3.28. Conclusion: The most likely interpretation of these observations is that a defect in the GLC1A glaucoma gene is not responsible for adult-onset primary open angle glaucoma in Family UM:POAG1. This suggests the existence of at least two primary open-angle glaucoma genes, the previously reported GLC1A gene on chromosome 1q and another gene located elsewhere in the genome. Diagnosis of UM:POAG1 glaucoma between ages 42 and 57 also raises questions about how the glaucoma present in this family is related to the common later-age onset form of the disease.

Duke Scholars

Author Elizabeth Rebecca Hauser Biostatistics & Bioinformatics