DO: 11830; MONDO: 0011300;
Cytogenetic location: 12q21-q23 Genomic coordinates (GRCh38) : 12:71,100,001-108,600,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 12q21-q23 | Myopia-3 | 603221 | Autosomal dominant | 2 |
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.
Young et al. (1998) reported a large German/Italian family segregating autosomal dominant high-grade myopia (refractive error greater than or equal to -6.00 diopters). The family had no clinical evidence of connective tissue abnormalities indicative of Stickler syndrome (108300) or Marfan syndrome (154700), both of which have myopia as a feature. The average age at diagnosis of myopia was 5.9 years. The average spherical component refractive error for the affected individuals was -9.47 diopters.
In a large German/Italian family segregating autosomal dominant high-grade myopia, Young et al. (1998) demonstrated linkage of the disorder to chromosome 12q21-q23. The maximum lod score with 2-point linkage analysis was 3.85 at a recombination fraction of 0.0010, for markers D12S1706 and D12S327. Recombination events defined a 30.1-cM interval on 12q21-q23 for this second autosomal myopia gene. Young et al. (1998) pointed to decorin (DCN; 125255), which maps to chromosome 12q23, and lumican (LUM; 600616), which maps to chromosome 12q21.3-q22, as candidate genes. These are members of the small interstitial proteoglycan family of proteins that are expressed in the extracellular matrix of various tissues. Both interact with collagen and limit the growth of fibril diameter. Dermatan sulfate proteoglycan-3 (DSPG3; 601657), which maps to 12q21, is another small interstitial proteoglycan that is expressed in cartilage, as well as in ligaments and the placental tissues. Young et al. (1998) suggested that fibrillogenesis of the sclera may be affected by mutations in these candidate proteins, as has been demonstrated in connective tissue disorders such as Stickler syndrome and Marfan syndrome.
Lin et al. (2010) analyzed 4 promoter SNPs (601T-C, -59CC/-, -628delA, -1554T-C) of the LUM gene for association with high myopia, defined as -6.5 diopters, in 182 affected Taiwanese Chinese individuals and 78 Taiwanese Chinese controls. They found significant differences in 4 haplotype distributions of the 4 SNPs between the 2 groups (corrected p values less than 2.3 x 10(-4)); stepwise regression analysis did not reveal any 1 of the 4 polymorphisms to have a greater effect on myopia than the others.
In a study of 201 Taiwanese Chinese individuals with high myopia and 86 matched controls, Lin et al. (2010) found that a SNP in the LUM gene, 1567C-T, showed a significant difference between patients and control subjects (p = 0.0016). Haplotype analysis revealed a significantly higher presence of this and previously identified LUM polymorphisms (Lin et al., 2010) in patients with myopia (p less than 0.0001). Lin et al. (2010) determined that the 1567T polymorphism has a lower reporter gene activity than that of 1567C.
In 265 multiplex myopia families with 1,023 affected individuals, including 628 individuals with high-grade myopia, Metlapally et al. (2010) performed genotyping using 13 SNPs in the candidate gene IGF1 (147440) on chromosome 12q22-q24.1. The rs6214 SNP in the 3-prime untranslated region of IGF1 showed significant association with both the high-grade myopia and any myopia phenotypes (corrected p = 0.002 for both).
Kaiser, P. K., Friedman, N. J., Pineda, R., II. The Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology. Vol. 2. Philadelphia: Saunders , 2004. P. 457.
Lin, H.-J., Kung, Y.-J., Lin, Y.-J., Sheu, J. J. C., Chen, B.-H., Lan, Y.-C., Lai, C.-H., Hsu, Y.-A., Wan, L., Tsai, F. J. Association of the lumican gene functional 3-prime-UTR polymorphism with high myopia. Invest. Ophthal. Vis. Sci. 51: 96-102, 2010. [PubMed: 19643966] [Full Text: https://doi.org/10.1167/iovs.09-3612]
Lin, H.-J., Wan, L., Tsai, Y., Chen, W.-C., Tsai, S.-W., Tsai, F.-J. The association between lumican gene polymorphisms and high myopia. Eye 24: 1093-1101, 2010. [PubMed: 20010793] [Full Text: https://doi.org/10.1038/eye.2009.254]
Metlapally, R., Ki, C.-S., Li, Y.-J., Tran-Viet, K.-N., Abbott, D., Malecaze, F., Calvas, P., Mackey, D. A., Rosenberg, T., Paget, S., Guggenheim, J. A., Young, T. L. Genetic association of insulin-like growth factor-1 polymorphisms with high-grade myopia in an international family cohort. Invest. Ophthal. Vis. Sci. 51: 4476-4479, 2010. [PubMed: 20435602] [Full Text: https://doi.org/10.1167/iovs.09-4912]
Young, T. L., Ronan, S. M., Alvear, A. B., Wildenberg, S. C., Oetting, W. S., Atwood, L. D., Wilken, D. J., King, R. A. A second locus for familial myopia maps to chromosome 12q. Am. J. Hum. Genet. 63: 1419-1424, 1998. [PubMed: 9792869] [Full Text: https://doi.org/10.1086/302111]