Myopia 19, Autosomal Dominant

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 susceptibility to myopia, see 160700.

Clinical Features

Ma et al. (2010) studied 11 affected individuals from a 4-generation Chinese family from Zhejiang province segregating autosomal dominant high myopia. The average age at diagnosis of myopia was 6.9 years (range, 4 to 11 years). The average spherical component refractive error for the affected individuals was -11.59 +/- 5.26 diopters (D) (range, -6.5 to -26 D). Mean axial length in highly myopic individuals was 29.17 +/- 1.50 mm (range, 26.80 to 31.42 mm) compared to 23.59 +/- 1.04 mm (range, 22.03 to 25.72 mm) in non-highly myopic family members. Ophthalmologic examination excluded known ocular diseases associated with myopia, including keratoconus (see 148300), spherophakia, ectopia lentis (see 129600), retinal dystrophy (see 268000), and optic atrophy (see 165500). Males and females were equally affected.

Mapping

In a 4-generation Chinese family segregating autosomal dominant high myopia, Ma et al. (2010) excluded known syndromic myopia loci, and linkage to known loci for nonsyndromic autosomal dominant high myopia was insignificant or suggestive only. Genomewide screening yielded a 2-point lod score of 3.02 at marker D5S419. Fine mapping with 13 flanking markers resulted in a significant lod score of 3.71 at marker D5S502 (theta = 0.0) on chromosome 5p15.1-p13.3. Recombination events narrowed the critical region to an approximately 11.69-cM (14.14-Mb) interval between D5S2096 and D5S1986. Ma et al. (2010) stated that the critical region identified in this family did not overlap with the locus previously found in 3 Hong Kong Chinese pedigrees with high myopia (MYP16; 612554) on chromosome 5p15.33-p15.2.

Molecular Genetics

In a 4-generation Chinese family segregating autosomal dominant high myopia mapping to chromosome 5p15.1-p13.3, Ma et al. (2010) analyzed 6 candidate genes, including CDH6 (603007), CDH10 (604555), CDH12 (600562), PDZD2 (610697), and GOLPH3 (612207), but did not identify any disease-causing mutation.