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SU Rehman, MD Mohamed, A Jacob, B Pal, JA Bradbury, CF Inglehearn; Genetic Analysis of a Pedigree with Foveal Hypoplasia and Variable Degees of Anterior Segment Dysgenesis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):819.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To carry out a preliminary genetic screen in a large consanguineous pedigree with foveal hypoplasia, and anterior segment dysgenesis of variable penetrance, but no other associated syndromic features. Methods: Eight members of a large consanguineous pedigree of Pakistani origin were examined. The disease segregated in an autosomal recessive pattern. Four affected individuals were seen, all presenting with nystagmus and poor vision. Clinical examination revealed foveal hypoplasia. Also, of note was the presence of posterior embryotoxon in one and Axenfeld's anomaly in another of the individuals. Genomic DNA samples from this pedigree were typed using microsatellite markers immediately adjacent to PAX6 at 11p13 (D11S1324), PITX2 at 4q25-q26 (D4S2940), and FOXC1 at 6q25 (D6S967). Data was analysed by two-point mapping across the regions of interest using the LINKAGE suite of programmes. Results: No evidence of linkage was seen with any of these markers. Exclusion of linkage was significant (lod scores < -2) to a distance of 10cM on either side of the PITX2 marker, 6cM on either side of the PAX6 marker and 3cM on either side of the FOXC1 marker. Conclusion: The phenotypic appearance of non-syndromic foveal hypoplasia and anterior segment dysgenesis most closely suggest a PAX6 mutation. Anterior segment dysgenesis is also associated with mutations in PITX2 and FOXC1. We have excluded linkage to all these loci. These results lend further evidence to locus heterogeneity of the described phenotype. A whole genome screen for linkage is warranted in this pedigree.
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