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E.D. Silva, J.M. Yang, L.C. Santos, O.H. Sundin; Recessive Nanophthalmos is Caused by Mutations of the Human Mfrp Gene in Two Portuguese Families . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4617.
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© ARVO (1962-2015); The Authors (2016-present)
To present the clinical and molecular characterization of 2 portuguese families with recessive nanophthalmos.
We identified three patients carrying the nanophthalmos phenotype in 2 unrelated portuguese families. Standard clinical exams included best corrected visual acuity, objective refraction, A– and B–scan ultrasound and electroretinographic evaluation. The entire coding region of the MFRP gene was sequenced using the ABI 3700.
We found MFRP mutations in the two portuguese families. In one, a boy age 9, was homozygous for an amber mutation in exon 5 at codon 175. His refraction was +13.5 right eye, and +13.0 left eye, with 20/80 best corrected acuity in each eye. His RPE showed no pigmentary anomalies. In two affected sisters from another pedigree, refractions and visual acuities were RE: +22.0, 20/40 ; LE: +22.0, 20/100. Each had patches of RPE hypopigmentation in the mid–periphery of the retina. They are both compound heterozygote for a frameshift deletion and an I182T substitution in exon 5 of MFRP. The three presumed null mutations truncated MFRP in either the first or second cubilin domain, and caused complete loss of the CRD domain. The point mutant I182T substituted a polar amino acid at an extremely conserved site.
We present two families with independent mutations in MFRP, a gene that is expressed in the eye and encodes a protein with homology to Tolloid and to the Wnt–binding domain of the Frizzled transmembrane receptors. This gene is not critical for retinal function, as patients entirely lacking MFRP can still have good refraction–corrected vision and clinically normal electroretinograms. MFRP appears primarily devoted to regulating axial length of the eye.
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