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Abstract #15909 Published in IGR 2-3
Chromosomal duplication involving the forkhead transcription factor gene FOXC1 causes iris hypoplasia and glaucoma
Lehmann OJ; Ebenezer ND; Jordan T; Fox M; Ocaka L; Payne A; Leroy BP; Clark BJ; Hitchings RA; Povey SAmerican Journal of Human Genetics 2000; 67: 1129-1135
The forkhead transcription factor gene FOXC1 (formerly FKHL7) is responsible for a number of glaucoma phenotypes in families in which the disease maps to 6p25, although mutations have not been found in all families in which the disease maps to this region. In a large pedigree with iris hypoplasia and glaucoma mapping to 6p25 (peak LOD score 6.20 (recombination fraction 0) at D6S967), no FOXC1 mutations were detected by direct sequencing. However, genotyping with microsatellite repeat markers suggested the presence of a chromosomal duplication that segregated with the disease phenotype. The duplication was confirmed in affected individuals by FISH with markers encompassing FOXC1. These results provide evidence of gene duplication causing developmental disease in humans, with increased gene dosage of either FOXC1 or other, as yet unknown genes within the duplicated segment being the probable mechanism responsible for the phenotype.
Dr. O.J. Lehmann, Department of Molecular Genetics, Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK
Classification:
1.2 Population genetics (Part of: 1 General aspects)
