Extreme hyperopia is the result of null mutations in MFRP, which encodes a Frizzled-related protein

Olof H. Sundin, Gregory S. Leppert, Eduardo D. Silva, Jun Ming Yang, Sharola Dharmaraj, Irene H. Maumenee, Luisa Coutinho Santos, Cameron F. Parsa, Elias I. Traboulsi, Karl W. Broman, Cathy DiBernardo, Janet S. Sunness, Jeffrey Toy, Ethan M. Weinberg

Research output: Contribution to journalArticlepeer-review

Abstract

Nanophthalmos is a rare disorder of eye development characterized by extreme hyperopia (farsightedness), with refractive error in the range of +8.00 to +25.00 diopters. Because the cornea and lens are normal in size and shape, hyperopia occurs because insufficient growth along the visual axis places these lensing components too close to the retina. Nanophthalmic eyes show considerable thickening of both the choroidal vascular bed and scleral coat, which provide nutritive and structural support for the retina. Thickening of these tissues is a general feature of axial hyperopia, whereas the opposite occurs in myopia. We have mapped recessive nanophthalmos to a unique locus at 11q23.3 and identified four independent mutations in MFRP, a gene that is selectively expressed in the eye and encodes a protein with homology to Tolloid proteases and 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, produce clinically normal electroretinograms, and show only modest anomalies in the dark adaptation of photoreceptors. MFRP appears primarily devoted to regulating axial length of the eye. It remains to be determined whether natural variation in its activity plays a role in common refractive errors.

Original languageEnglish (US)
Pages (from-to)9553-9558
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number27
DOIs
StatePublished - Jul 5 2005

Keywords

  • Eye
  • Genetics
  • Morphology
  • Nanophthalmos

ASJC Scopus subject areas

  • General

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