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. 1998 Nov;63(5):1419–1424. doi: 10.1086/302111

A second locus for familial high myopia maps to chromosome 12q.

T L Young 1, S M Ronan 1, A B Alvear 1, S C Wildenberg 1, W S Oetting 1, L D Atwood 1, D J Wilkin 1, R A King 1
PMCID: PMC1377552  PMID: 9792869

Abstract

Myopia, or nearsightedness, is the most common eye disorder worldwide. "Pathologic" high myopia, or myopia of <=-6.00 diopters, predisposes individuals to retinal detachment, macular degeneration, cataract, or glaucoma. A locus for autosomal dominant pathologic high myopia has been mapped to 18p11.31. We now report significant linkage of high myopia to a second locus at the 12q21-23 region in a large German/Italian family. The family had no clinical evidence of connective-tissue abnormalities or glaucoma. 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. Markers flanking or intragenic to the genes for the 18p locus, Stickler syndromes type I and II (12q13.1-q13.3 and 6p21.3), Marfan syndrome (15q21.1), and juvenile glaucoma (chromosome 1q21-q31) showed no linkage to the myopia in this family. The maximum LOD score with two-point linkage analysis in this pedigree was 3.85 at a recombination fraction of .0010, for markers D12S1706 and D12S327. Recombination events identified markers D12S1684 and D12S1605 as flanking markers that define a 30.1-cM interval on chromosome 12q21-23, for the second myopia gene. These results confirm genetic heterogeneity of myopia. The identification of this gene may provide insight into the pathophysiology of myopia and eye development.

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Selected References

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  1. Bianco P., Fisher L. W., Young M. F., Termine J. D., Robey P. G. Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues. J Histochem Cytochem. 1990 Nov;38(11):1549–1563. doi: 10.1177/38.11.2212616. [DOI] [PubMed] [Google Scholar]
  2. Chakravarti S., Stallings R. L., SundarRaj N., Cornuet P. K., Hassell J. R. Primary structure of human lumican (keratan sulfate proteoglycan) and localization of the gene (LUM) to chromosome 12q21.3-q22. Genomics. 1995 Jun 10;27(3):481–488. doi: 10.1006/geno.1995.1080. [DOI] [PubMed] [Google Scholar]
  3. Deere M., Johnson J., Garza S., Harrison W. R., Yoon S. J., Elder F. F., Kucherlapati R., Hook M., Hecht J. T. Characterization of human DSPG3, a small dermatan sulfate proteoglycan. Genomics. 1996 Dec 15;38(3):399–404. doi: 10.1006/geno.1996.0643. [DOI] [PubMed] [Google Scholar]
  4. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  5. Fasman K. H., Cuticchia A. J., Kingsbury D. T. The GDB Human Genome Data Base anno 1994. Nucleic Acids Res. 1994 Sep;22(17):3462–3469. doi: 10.1093/nar/22.17.3462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
  7. Hedbom E., Heinegård D. Interaction of a 59-kDa connective tissue matrix protein with collagen I and collagen II. J Biol Chem. 1989 Apr 25;264(12):6898–6905. [PubMed] [Google Scholar]
  8. Hedlund H., Mengarelli-Widholm S., Heinegård D., Reinholt F. P., Svensson O. Fibromodulin distribution and association with collagen. Matrix Biol. 1994 Apr;14(3):227–232. doi: 10.1016/0945-053x(94)90186-4. [DOI] [PubMed] [Google Scholar]
  9. Kruglyak L., Daly M. J., Reeve-Daly M. P., Lander E. S. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet. 1996 Jun;58(6):1347–1363. [PMC free article] [PubMed] [Google Scholar]
  10. Lander E. S., Green P. Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2363–2367. doi: 10.1073/pnas.84.8.2363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nowacki P. M., Byck S., Prevost L., Scriver C. R. PAH Mutation Analysis Consortium Database: 1997. Prototype for relational locus-specific mutation databases. Nucleic Acids Res. 1998 Jan 1;26(1):220–225. doi: 10.1093/nar/26.1.220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rada J. A., Achen V. R., Perry C. A., Fox P. W. Proteoglycans in the human sclera. Evidence for the presence of aggrecan. Invest Ophthalmol Vis Sci. 1997 Aug;38(9):1740–1751. [PubMed] [Google Scholar]
  13. Rada J. A., Cornuet P. K., Hassell J. R. Regulation of corneal collagen fibrillogenesis in vitro by corneal proteoglycan (lumican and decorin) core proteins. Exp Eye Res. 1993 Jun;56(6):635–648. doi: 10.1006/exer.1993.1081. [DOI] [PubMed] [Google Scholar]
  14. Schwartz M., Haim M., Skarsholm D. X-linked myopia: Bornholm eye disease. Linkage to DNA markers on the distal part of Xq. Clin Genet. 1990 Oct;38(4):281–286. [PubMed] [Google Scholar]
  15. Sperduto R. D., Seigel D., Roberts J., Rowland M. Prevalence of myopia in the United States. Arch Ophthalmol. 1983 Mar;101(3):405–407. doi: 10.1001/archopht.1983.01040010405011. [DOI] [PubMed] [Google Scholar]
  16. Stewart E. A., McKusick K. B., Aggarwal A., Bajorek E., Brady S., Chu A., Fang N., Hadley D., Harris M., Hussain S. An STS-based radiation hybrid map of the human genome. Genome Res. 1997 May;7(5):422–433. doi: 10.1101/gr.7.5.422. [DOI] [PubMed] [Google Scholar]
  17. Young T. L., Ronan S. M., Drahozal L. A., Wildenberg S. C., Alvear A. B., Oetting W. S., Atwood L. D., Wilkin D. J., King R. A. Evidence that a locus for familial high myopia maps to chromosome 18p. Am J Hum Genet. 1998 Jul;63(1):109–119. doi: 10.1086/301907. [DOI] [PMC free article] [PubMed] [Google Scholar]

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