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Francois J. Malecaze, Nicolas Chassaing, Alexandre Causse, Andrée Delahaye, Adeline Vigouroux, Patrick Calvas; Molecular Basis of Microphthalmia/Anophthalmia in Human. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1540.
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Microphthalmia/Anophthalmia (M/A) are the most severe ocular developmental defects corresponding to a reduce size or an absence of the ocular globe. Incidence of M/A is estimated to be 1/10.000. Numerous genes have been implicated either in non syndromic and syndromic forms of M/A. The aim of this study was to evaluate respective responsibility of participation of the 7 major genes involved in M/A in human.
120 patients suffering from M/A were included in this study. Mutations screening was conducted in SOX2, PAX6, OTX2, RAX, FOXE3, CHX10, and GDF6 entire coding regions and intron-exon borders by direct sequencing. Furthermore, we developed a semi-quantitative approach (QMPSF) in order to detect deletion or duplication events for SOX2, PAX6, OTX2, RAX, and CHX10. Mutated patients’ phenotypes were examined in order to obtain a better delineation of each gene phenotypic spectrum.
Point mutations were identified in SOX2 (12 patients), OTX2 (3 patients), RAX (3 patients), FOXE3 (2 patients), CHX10 (1 patient), and GDF6 (1 patient). In addition, five heterozygous deletions of SOX2, 2 heterozygous deletions of OTX2 and 1 heterozygous deletion of RAX were identified.
This is the largest cohort of patients for whom a systematic screening of known M/A genes is reported. Screening allows identification of the molecular defects in one quarter (30/120) of patients. We provide a rough evaluation of the frequency of these genes involvement in M/A and recognized some unusual phenotypes. Finally, these results underline the genetic heterogeneity of M/A and as the majority of patients do not harbour mutations in known M/A genes other genes remain to be identified.
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