Familial Glaucoma Iridogoniodysplasia Maps to a 6p25 Region Implicated in Primary Congenital Glaucoma and Iridogoniodysgenesis Anomaly

Abstract

Familial glaucoma iridogoniodysplasia (FGI) is a form of open-angle glaucoma in which developmental anomalies of the iris and irido-corneal angle are associated with a juvenile-onset glaucoma transmitted as an autosomal dominant trait. A single large family with this disorder was examined for genetic linkage to microsatellite markers. A peak LOD score of 11.63 at a recombination fraction of 0 was obtained with marker D6S967 mapping to chromosome 6p25. Haplotype analysis places the disease gene in a 6.4-cM interval between the markers D6S1713 and D6S1600. Two novel clinical appearances extend the phenotypic range and provide evidence of variable expressivity. The chromosome 6p25 region is now implicated in FGI, primary congenital glaucoma, and iridogoniodysgenesis anomaly. This may indicate the presence of a common causative gene or, alternatively, a cluster of genes involved in eye development/function.

The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25

“…The most tightly linked markers for these disorders (D6S344 and D6S967) have been localized to the same YAC (954h10) as FKHL7. The possibility that these phenotypes are allelic has been raised previously 14 . Evidence for this comes from the finding that mutations in PITX2 can cause both RIEG1 and IRID2 (refs 6,7).…”

“…In addition, a group of dominant disorders involving changes in the anterior segment of the eye have been mapped to 6p25 (refs 12−15). These disorders all have glaucoma as part of their phenotype and have been postulated to be allelic 14 .…”

Late-Onset Macular Degeneration and Long Anterior Lens Zonules Result from aCTRP5Gene Mutation

“…4,9,10,[25][26][27][28][29][30] Similarly, for the LAZ phenotype, we excluded the loci for pigmentary dispersion syndrome, Marfan syndrome, pseudoexfoliation syndrome, and previously mapped glaucoma loci. 28,[31][32][33][34][35] Further, more than 90% of the genome was excluded before identifying positive lod scores, indicating linkage on the long arm of chromosome 11 for both LAZ and macular degeneration.…”

Rieger syndrome: a clinical, molecular, and biochemical analysis

“…One patient has been reported with the central corneal opacity typical of Peters anomaly who also had a mutation in PITX2 [32]. glaucoma iridogoniodysplasia [37][38][39][40][41]. Iridogoniodysgenesis and familial glaucoma iridogoniodysplasia are described as having iris hypoplasia, iridocorneal angle abnormalities, and glaucoma.…”