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RV Jamieson, R Perveen, B Kerr, M Carette, N Farrar, D Donnai, F Munier, GC M Black; MAF Mutation and Translocation in Human Cataract and Anterior Segment Abnormality . Invest. Ophthalmol. Vis. Sci. 2002;43(13):477.
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Purpose: We identified a family with cataract and anterior segment abnormality co-segregating with a chromosomal translocation t(5;16)(p15.3;q23.2). We hypothesised that this identified a gene with a developmental role in the lens and anterior segment. Methods: Somatic cell hybrids were established and translocation breakpoints identified by STS analysis of BAC contigs across the breakpoints. A candidate gene was identified and mutation screening of this gene in other individuals and families with cataract and anterior segment dysgenesis was performed. Results: Cloning the 16q23.2 breakpoint in the translocation family identified a break through the genomic-control domain of MAF, a basic region leucine zipper (bZIP) transcription factor, expressed in mammalian lens development. Individuals with the balanced translocation in this pedigree have juvenile-onset cataracts. Individuals with the unbalanced translocation 46,XX,der(5),t(5;16)(p15.3;q23.2) have congenital cataracts, as well as more severe ocular phenotypes including Peters anomaly. Screening of other families and individuals with congenital cataract has identified a mutation in MAF in a family where there are individuals with juvenile-onset cataract, microcornea and iris coloboma. This mutation, R288P, is in the highly evolutionarily conserved DNA-binding domain of MAF. The mutation cosegregates with disease in the family and is not present in 496 normal control chromosomes. Conclusion: We have identified two families with findings indicating that the lens development gene, MAF, is a human disease gene in cataract and anterior segment abnormality. Since Maf expression occurs in the developing lens, the association with anterior segment abnormalities in these families emphasises the importance of the lens in anterior segment development. The finding of iris coloboma in one of the families broadens the possible role of MAF in anterior segment development.
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