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J. C. Zenteno, M. A. Quiroz-Gonzalez, F. Graue-Wiechers; A New Family With the Nanophthalmos-Retinitis Pigmentosa Complex Caused by Compound Heterozygous Mutations in the MFRP Gene. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3740.
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The syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen is a distinct autosomal recessive entity recently identified in two unrelated families from Mexico and Spain. The disease is caused by homozygous truncating mutations in MFRP, a gene located at chromosome 11q13 and encoding a membrane receptor with a potential role in the WNT pathway. This entity has emerged as a novel form of syndromic retinitis pigmentosa. We describe the ophthalmologic and genetic features of a novel Mexican family with the disease
Two affected brothers (aged 18 and 16 years) were studied. Their parents were not consanguineous. 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 both affected subjects and direct nucleotide analysis was performed using fluorescent dideoxy-chain terminators.
Both affected siblings had high hyperopia (+16 diopters). 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 14.65 mm to 14.93 mm) and optic disc drusen. OCT imaging showed increased macular thickening as well as macular cysts. MFRP gene molecular analysis disclosed the presence of two MFRP mutations: a heterozygous 1-bp deletion (c.498delC) in exon 5, predicting a prematurely truncated protein (P166fsX190), and a novel heterozygous point mutation from C to A, predicting a nonsense change from Tyrosine (TAC) to a stop signal (TAA), at codon 317.
This work describes the clinical and genetic characteristics of the third known family with the syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen. These are the youngest individuals reported to date with the syndrome and we demonstrate for the first time that compound heterozygosity for MFRP mutations can be a source of the disease.
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