DO: 11830; MONDO: 0013604;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p22.2 | Myopia 21, autosomal dominant | 614167 | Autosomal dominant | 3 | ZNF644 | 614159 |
A number sign (#) is used with this entry because of evidence that myopia-21 (MYP21) is caused by heterozygous mutation in the ZNF644 gene (614159) on chromosome 1p22.
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.
Shi et al. (2011) studied 6 patients from a 5-generation Han Chinese family segregating autosomal dominant severe high myopia. (High myopia is defined as a spherical refractive error greater than or equal to -6.00 diopters.) Disease onset was at 3 to 4 years of age, with all affected individuals developing high myopia by age 7 years. Three elderly patients showed typical fundus features of high myopia, with thinning of the retinal pigment epithelium and the choriocapillaris that resulted in the so-called 'tigroid' or 'tessellated' appearance of the fundus.
The transmission pattern of high myopia in the Han Chinese family reported by Shi et al. (2011) was consistent with autosomal dominant inheritance.
In a 5-generation Han Chinese family segregating autosomal dominant high myopia, Shi et al. (2011) performed exome sequencing and segregation analysis and identified a missense mutation in the ZNF644 gene (S672G; 614159.0001). A lod score of 3.19 was obtained (theta = 0.0) for autosomal dominant inheritance with full penetrance and 0.0001 for the disease allele frequency. Analysis of ZNF644 in an additional 300 unrelated sporadic Han Chinese patients with high myopia revealed 5 heterozygous mutations in 11 patients, respectively (see, e.g., 614159.0002-614159.0003), that were not found in 600 ethnically matched controls .
By Sanger sequencing, Tran-Viet et al. (2012) screened for mutations in the ZNF644 gene in a cohort of 131 U.S. patients with high-grade myopia. In 2 individuals, one Caucasian and the other African American, they identified a heterozygous mutation (T242M and E274V, respectively). The variants were not found in 1,344 and 100 ethnically matched chromosomes, respectively; however, due to lack of additional family members for both individuals, segregation analysis was not possible.
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.
Shi, Y., Li, Y., Zhang, D., Zhang, H., Li, Y., Lu, F., Liu, X., He, F., Gong, B., Cai, L., Li, R., Liao, S., and 17 others. Exome sequencing identifies ZNF644 mutations in high myopia. PLoS Genet. 7: e1002084, 2011. Note: Electronic Article. [PubMed: 21695231] [Full Text: https://doi.org/10.1371/journal.pgen.1002084]
Tran-Viet, K.-N., St. Germain, E., Soler, V., Powell, C., Lim, S.-H., Klemm, T., Saw, S. M., Young, T. L. Study of a US cohort supports the role of ZNF644 and high-grade myopia susceptibility. Molec. Vision 18: 937-944, 2012. [PubMed: 22539872]