A new phenotype of recessively inherited Foveal Hypoplasia and Anterior Segment Dysgenesis maps to a locus on chromosome 16q23.2–24.2.

Abstract

Abstract: : Purpose:To document in a large consanguineous pedigree an unusual and previously unreported phenotype of recessively inherited foveal hypoplasia, occurring together with anterior segment dysgenesis of variable penetrance. In addition, to locate the defective gene underlying this disorder by linkage analysis. Methods:Affected individuals were subjected to an ophthalmic examination and blood samples were obtained. Genetic markers covering the entire genome at an average spacing of 9 cM were genotyped in genomic DNA from family members in order to identify a linked region. The coding sequence of the FOXC2 gene was screened for mutations in affected individuals. Results:Five members of the pedigree presented with nystagmus and poor vision. Ophthalmic examination revealed foveal hypoplasia and anterior segment dysgenesis in all cases. Linkage analysis identified a region on chromosome 16q23–24 that showed significant linkage with the disease in this family. Multipoint analysis generated a LOD score of 5.51 at D16S511. Recombination events defined a 22.1 cM/6.5 mb interval between markers D16S3098 and D16S2621, which includes the transcription factor FOXC2. However, sequencing of this single exon gene in patients’ DNA revealed no mutations. Conclusions:A new phenotype consisting of foveal hypoplasia and anterior segment dysgenesis with recessive inheritance is documented. The combination of developmental abnormalities in both anterior and posterior eye structures suggests a defect in early ocular development and morphogenesis. Linkage analysis mapped the gene defect to a locus at chromosome 16q23.2–24.2.

Keywords: genetics • gene mapping • retina