Extreme hyperopia is the result of null mutations in MFRP, which encodes a Frizzled-related protein.
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 electro-retinograms, 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.
Laboratory of Developmental Genetics, The Johns Hopkins University, Baltimore, MD 21287, USA. osundin@jhmi.edu
Olof H
OH
Sundin
Gregory S
GS
Leppert
Eduardo D
ED
Silva
Jun-Ming
JM
Yang
Sharola
S
Dharmaraj
Irene H
IH
Maumenee
Luisa Coutinho
LC
Santos
Cameron F
CF
Parsa
Elias I
EI
Traboulsi
Karl W
KW
Broman
Cathy
C
Dibernardo
Janet S
JS
Sunness
Jeffrey
J
Toy
Ethan M
EM
Weinberg
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D003623:Dark Adaptation / Q000235:genetics; D004596:Electroretinography; D005123:Eye / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D005808:Genes, Recessive / Q000235:genetics; D008040:Genetic Linkage; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006956:Hyperopia / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA; D014463:Ultrasonography; D000099274:Frizzled-Related Proteins
D008565:Membrane Proteins; C490110:MFRP protein, human; D000099274:Frizzled-Related Proteins