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J. M. Gonzalez, E. L. Pelcastre, J. L. Tobilla-Canales, E. Garcia-Ortiz, M. Amato-Almanza, C. Villanueva-Mendoza, Z. Espinoza-Mattar, J. C. Zenteno; Mutational Analysis of CHX10, GDF6, OTX2, RAX, and SOX2 Genes in 50 Unrelated Microphthalmia-Anophthamia-Coloboma (MAC) Spectrum Cases from Mexico. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3076.
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© ARVO (1962-2015); The Authors (2016-present)
Microphthalmia, anophthalmia, and coloboma (MAC) are congenital eye malformations causing a significant percentage of visually impaired children. Although these anomalies can occasionally arise from prenatal exposure to chemical or biological teratogens, mutations in well defined genes originate monogenic, potentially heritable, forms of MAC. Thus, mutations in genes as CHX10, GDF6, RAX, SOX2, and OTX2, among others, have been recognized in autosomal dominant or recessive forms of MAC. Available data indicates that SOX2 and OTX2 are the two most commonly mutated genes in monogenic MAC. However, as more numerous samples of MAC subjects from distinct ancestries would be analyzed, it is expected that a better estimation of the actual involvement of specific MAC-genes could be made. We report the results of a comprehensive mutational analysis of MAC related genes in a large cohort of unrelated MAC Mexican subjects.
All patients underwent detailed ophthalmologic examination to classify the eye malformation. Molecular analysis included PCR amplification and automated direct sequencing of the complete coding region of CHX10, GDF6, RAX, SOX2, and OTX2 genes.
A total of 8 mutations (16% prevalence), 4 of them novel, were recognized. Molecular defects included 4 GDF6 mutations (1 novel), 2 novel RAX mutations, 1 novel OTX2 mutation, and 1 SOX2 mutation. Anophthalmia and nanophthalmia, two ocular anomalies not previously associated to GDF6 mutations, were observed in two subjects from our cohort carrying GDF6 defects, thus expanding the spectrum of ocular anomalies caused by mutations in this gene.
Our study underscores the importance of genotyping large groups of patients from distinct ethnic origins for improving the estimation of the global involvement of particular MAC-causing genes.
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