Primary congenital glaucoma localizes to chromosome 14q24.2-24.3 in two consanguineous Pakistani families

Abstract

Purpose: Two consanguineous Pakistani families with autosomal recessive primary congenital glaucoma were recruited to identify the disease locus.

Methods: Ophthalmic examinations including slit lamp biomicroscopy and applanation tonometry were employed to classify the phenotype. Blood samples were collected and genomic DNA was extracted. A genome wide scan was performed on both families with 382 polymorphic microsatellite markers. Two point LOD scores were calculated, and haplotypes were constructed to define the disease interval.

Results: Clinical records and ophthalmic examinations suggest that affected individuals in families PKGL005 and PKGL025 have primary congenital glaucoma. Maximum two-point LOD scores of 5.88 with D14S61 at theta=0 and 6.19 with D14S43 at theta=0 were obtained for families PKGL005 and PKGL025, respectively. Haplotype analysis defined the disease locus as spanning a 6.56 cM (~4.2 Mb) genetic interval flanked by D14S289 proximally and D14S85 distally.

Conclusions: Linkage analysis localizes autosomal recessive primary congenital glaucoma to chromosome 14q24.2-24.3 in consanguineous Pakistani families.

Figure 1

Pedigree of families PKGL005 and PKGL025. Squares denote males, circles indicate females, filled symbols represent affected individuals, double lines between individuals indicate consanguinity, and a diagonal line through a symbol signify that the family member is deceased. The haplotypes of 15 adjacent chromosome 14q14.2–24.3 microsatellite markers for families PKGL005 (A) and family PKGL025 (B) are shown with alleles forming the risk haplotype shaded black, alleles cosegregating with primary congenital glaucoma (PCG) but not showing homozygosity shaded gray, and alleles not cosegregating with PCG shown in white.

Figure 2

Schematic representation of linkage on chromosome 14q24.2–24.3 in families PKGL005 and PKGL025. Filled circles denote STR markers, and solid vertical lines represent the chromosomal intervals in which markers are homozygous for affected members of each of the two families.