Nanophthalmos is a rare developmental disorder in which the eye is much smaller than normal, and the retina is placed unusually close to the lens. The result of this is profound hyperopia (farsightedness) in the range of +8 to +24 diopters, a condition apparent at birth and maintained throughout life. The eye is formed intact and functional, typically without disorders elsewhere in the body. This is in contrast to microphthalmia, in which small eyes are associated with more serious structural malformations. The nanophthalmic eye exhibits a thick iris and a lens displaced towards the anterior chamber, features thought to contribute to the high incidence of angle closure glaucoma among these patients. Another characteristic of the disease is massive thickening of the choroid and sclera, which may be associated with a tendency of the eye to develop exudative retinal detachment, especially as a complication of glaucoma or cataract surgery. The disease is usually inherited as an autosomal recessive. There is also an autosomal dominant form of the disease, which has recently been mapped by genetic linkage to an interval on chromosome 11p. The identity of this gene remains unknown, and no locus has yet been reported for the recessive form of the disease. This application focuses on detailed linkage mapping and isolation of the gene for recessive nanophthalmos. Once this is accomplished, we will investigate its pattern of expression and the subcellular localization of the gene product. Identification of a gene for nanophthalmos would provide a starting point for the genetic diagnosis and rational development of treatments for this rare ocular disease. It also promises insights into the developmental mechanisms by which the eye normally regulates its size and shape in order to adjust its optical properties.
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