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J. C. Zenteno, J. Crespí, J. A. Buil, F. Bassagañas, R. Ayala-Ramirez; A Novel Familial Frameshift Mutation Confirms MFRP as the Gene Responsible for the Syndrome of Posterior Microphthalmos-Renititis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3108.
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Posterior microphthalmos is defined by reduced total axial length in the presence of a normal sized cornea. Microphthalmic eyes have an axial length of 13-18.5 mm, refractive defects ranging between +8.00 to +25.00 diopters, and are associated with thickening of both the choroidal vascular bed and sclera. In a consanguineous Mexican family with a new autosomal recessive syndromic entity characterized by posterior microphthalmos, retinitis pigmentosa, foveoschisis, and optic disc drusen, Ayala-Ramirez et al. (2006) identified homozygosity for a 1-bp insertion in MFRP (membrane-type Frizzled-Related Protein), a gene previously implicated in isolated autosomal recessive nanophthalmos. We describe the clinical and molecular features of a new consanguineous family from Spain family with this particular syndrome.
Three affected brothers were studied. Their parents, who were first cousins, as well as 6 siblings were healthy. In affected brothers, complete ophthalmologic examinations were performed, including slit lamp biomicroscopy, funduscopy, ERG, fluorescein angiography (FA), A- and B-mode ultrasonography, and optical coherence tomography (OCT). The complete coding sequence of the MFRP gene was amplified in DNA from blood leukocytes of each affected subject and direct nucleotide analysis was performed using fluorescent dideoxy-chain terminators.
The three affected siblings had high hyperopia and normal corneal diameters. Funduscopy, ERG and FA demonstrated a progressive retinal dystrophy classified as retinitis pigmentosa. A- and B-mode ultrasonography evidenced diminished axial eye length (ranging from 14.72 mm to 16.08 mm) and optic disc drusen. OCT imaging showed macular retinoschisis in the three subjects in addition to macular edema in two of them. MFRP gene molecular analysis demonstrated a one base pair deletion in exon 5 (c.644delC) in all affected individuals, a change that predicts a truncated protein (P166fsX190). Parental DNA was not available.
The Spanish family described here confirms that the syndrome of posterior microphthalmos, retinitis pigmentosa, foveoschisis and optic disc drusen is a discrete autosomal recessive entity. This is the second family described so far with this phenotype and the frameshift mutation identified in the three affected subjects confirms MFRP as the gene responsible for this distinct ocular clinical association.
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