A gene for primary congenital glaucoma is not linked to the locus on chromosome 1q for autosomal dominant juvenile-onset open angle glaucoma

Background: Primary congenital glaucoma is an uncommon autosomal recessive condition that results from a developmental defect in the trabecular meshwork and anterior chamber angle, manifesting in the neonatal or infantile period with increased intraocular pressure, corneal enlargement and edema, and optic nerve cupping with consequent loss of vision. Nothing is known about its genetic location. Patients and Methods: Linkage analysis was performed in 25 primary congenital glaucoma Saudi Arabian families with six polymorphic DNA markers on chromosome 1q in a region that has shown tight linkage to a locus for autosomal dominant juvenile-onset open angle glaucoma (GLC1A). Twenty-four of these families are highly consanguineous. Results: Each family was shown separately to exclude the 8-centimorgan (cM) interval containing the GLC1A locus, Four families independently demonstrated overlapping regions of exclusion (theta less than or equal to -2) that spanned the entire 8-cM interval. Assignment of a primary congenital glaucoma locus in this region could be excluded by a cadre of 21 families because a primary congenital glaucoma disease locus did not segregate in an autosomal recessive manner on haplotypes constructed with markers in this region. For all families, no affected individuals demonstrated homozygosity of alleles in regions tightly linked to the GLC1A locus. Conclusion: These results exclude the 8-cM region on chromosome Iq shown to contain the GLCIA locus from containing a disease locus for primary congenital glaucoma in this population of 25 Saudi Arabian families.