Myopia 1, X-Linked

Description

Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004).

For a discussion of genetic heterogeneity of myopia, see 160700.

Clinical Features

Bartsocas and Kastrantas (1981) presented a convincing X-linked pedigree in which 3 myopic brothers had 5 grandsons, through daughters, with myopia. Some of the carrier females had mild myopia ('not requiring corrective glasses'). Although the proband, aged 6.5 years, had short stature, none of the other affected males were short or had hemeralopia or other ocular or physical abnormalities. (See 310500 for a discussion of the use of the terms hemeralopia vs nyctalopia.)

Ratnamala et al. (2011) described 2 large multigeneration Asian Indian pedigrees with isolated, nonsyndromic myopia in which the condition appeared to segregate as an X-linked recessive trait. The degree of myopia was variable in both families, ranging from -6 to -23 D (mean, -8.48 D). Only males were affected. Onset occurred between ages 4 and 12 years. No other associated visual anomalies, specifically color vision defect or night blindness, were present in any member of either pedigree.

Inheritance

Wold (1949) suggested X-linked recessive inheritance of one form of myopia. The pedigree pattern in the family reported by Ratnamala et al. (2011) was consistent with X-linked recessive inheritance with full penetrance.

Mapping

By 2-point linkage analysis in 2 families with isolated myopia, Ratnamala et al. (2011) found a maximum lod score of 5.3 for marker DXYS154, located in the pseudoautosomal region of distal Xq28 (PAR2), at a recombination fraction theta of 0.0. Thus, myopia in these families mapped to a region of Xq28 previously identified in a Danish family with Bornholm eye disease (BED; 300843). Haplotype analysis in 1 of the Indian families reduced the previously defined genomic interval of 6.8 cM at chromosome Xq27.3-q28 to approximately 1.4 cM by flanking the proximal marker at DXS1073 and the distal boundary at DXYS154.

Molecular Genetics

In the critical region on Xq28 identified for isolated myopia in 2 Indian families, Ratnamala et al. (2011) searched for mutations in exons and splice junctions of 13 candidate genes but did not detect any pathogenic variant.