Article | Published:

Mapping a gene for congenital fibrosis of the extraocular muscles to the centromeric region of chromosome 12

Abstract

Congenital Fibrosis of the Extraocular Muscles (CFEOM) is an autosomal dominant, ocular disorder characterized by congenital, nonprogressive, bilateral ptosis and external ophthalmoplegia. The pathophysiology of this disorder is unknown and it is unclear if it has a primary neurogenic or myopathic etiology. We report linkage of this disorder, in two unrelated families, to markers in the pericentromeric region of human chromosome 12. D12S59 does not recombine with the disease giving a two–point lod score of 12.5 (θ = 0.00). D12S87 and D12S85 flank the CFEOM locus with two–point lod scores of 8.9 (θ = 0.03) and 5.4 (θ = 0.03) respectively, defining a region of 8 cM. These data establish a map location for CFEOM and demonstrate that this may be a genetically homogeneous disorder.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Ringel, S.P., Wilson, W.B., Barden, M.T. & Kaiser, K.K. Histochemistry of human extraocular muscle. Arch. Ophthalmol. 96, 1067–1072 (1978).

  2. 2

    Oda, K. Motor innervation and acetylcholine receptor distribution of human extraocular muscle fibres. J. neurol. Sci. 74, 125–133 (1986).

  3. 3

    Kaminski, H.J., al Hakim, M., Leigh, R.J., Katirji, M.B. & Ruff, R.L. Extraocular muscles are spared in advanced Duchenne dystrophy. Ann. Neurol. 32, 586–588 (1992).

  4. 4

    Prendergast, R.A. et al. Relative sparing of extraocular muscles in Duchenne muscular dystrophy. Invest. ophth. vis. Sci. (Supp) 34, 1120 (1993).

  5. 5

    Kosmorsky, G. & Johns, D.R. Neuro–ophthalmologic manifestations of mitochondrial DNA disorders: chronic progressive external ophthalmoplegia, Keams-Sayre syndrome, and Leber's hereditary optic neuropathy. Neurol. Clin. 9, 147–161 (1991).

  6. 6

    Rowland, L.P. Progressive external opthalmoplegia and ocular myopathies. in Handbook of Clinical Neurology: Myopathies (eds Rowland, L.P. & DiMauro, S.) 287–329 (Elsevier Science Publishers B.V., Amsterdam, 1992).

  7. 7

    Harley, R.D., Rodrigues, M.M. & Crawford, J.S. Congenital fibrosis of the extraocular muscles. J. pediatr. ophthalmol. Strabismus 15, 346–358 (1978).

  8. 8

    Hiatt, R.L. & Halle, A.A. General fibrosis syndrome. Ann. Ophthalmol. 15, 1103–1109 (1983).

  9. 9

    Hansen, E. Congenital general fibrosis of the extraocular muscles. Acta. Ophthalmol. (Copenh) 46, 469–476 (1968).

  10. 10

    Brodsky, M.C., Pollock, S.C. & Buckley, E.G. Neural misdirection in congenital ocular fibrosis syndrome: implications and pathogenesis. J. pediat. ophthalmol. Strabismus 26, 159–161 (1989).

  11. 11

    Lawford, J.B. Congenital hereditary defect of ocular movements. Trans. ophthalmol. Soc. U.K. 8, 262–274 (1888).

  12. 12

    Houtman, W.A., van Weeden, T.W., Robinson, P.H., deVires, B. & Hoogenraad, T.U. Hereditary congenital external ophthalmoplegia. Ophthalmologica 193, 207–218 (1986).

  13. 13

    Rumph, M. Fibrose du muscle droit Inferieur, anomalies d'insertions et aplasies musculaires, une cause rare de troubles hereditaires non progressifs et congenltaux de la motilite oculaire. Ann. Oculistique 207, 831–829 (1974).

  14. 14

    Crawford, J.S. Congenital fibrosis syndrome. Can. J. Ophthalmol. 5, 331–336 (1970).

  15. 15

    Laughlin, R.C. Congenital fibrosis of the extraocular muscles; a report of six cases. Amer. J. Ophthalmology 41, 432–438 (1956).

  16. 16

    Brown, H.W. in Strabismus Ophthalmic Symposium (ed. Allen, J.H.) 205–236 (C.V. Mosby, St. Louis, 1950).

  17. 17

    Appleton, R.E., Chitayat, D., Jan, J.E., Kennedy, R. & Hall, J.G. Joubert's syndrome associated with congenital ocular fibrosis and histidinemia. Arch. Neurol. 46, 579–582 (1989).

  18. 18

    Kalpakian, B., Bateman, B.J., Sparkes, R.S. & Wood, G.K. Congenital ocular fibrosis syndrome associated with the Prader-Willi syndrome. J. pediat. ophthalmol. Strabismus 23, 170–173 (1986).

  19. 19

    Nemet, P., Godel, V., Ron, S. & Lazar, M. Ocular congenital fibrosis syndrome. Metab. pediatr. syst. Ophthalmol. 8, 172–174 (1985).

  20. 20

    Mutirangura, A., Ledbetter, S.A., Kuwano, A., Chinault, A.C. & Ledbetter, D.H. Dinucleotide repeat polymorphism at the GABAA receptor beta 3 (GABRB3) locus In the Angelman/Prader-Willi region (AS/PWS) of chromosome 15. Hum. molec. Genet. 1, 67 (1992).

  21. 21

    NIH/CEPH Collaborative Mapping Group. A comprehensive genetic linkage map of the human genome. Science 258, 67–86 (1992).

  22. 22

    Weissenbach, J. et al. A second-generation linkage map of the human genome. Nature 359, 794–801 (1992).

  23. 23

    Holt, M. et al. An index linkage map for human chromosome 12. Am. J. hum. Genet. 53, A1016 (1993).

  24. 24

    Matise, T.C., Perlin, M. & Chakravarti, A. Automated construction of genetic linkage maps using an expert system (MultiMap): a human genome linkage map. Nature Genet. 6, 384–390 (1994).

  25. 25

    Craig, I., Gemmill, R. & Kucherlapati, R. Report of the first international workshop on human chromosome 12 mapping. Cytogenet. Cell Genet. 61, 243–251 (1992).

  26. 26

    Jones, C. & Moore, E.E. Localization of a gene which complements branched-chain amino acid transaminase deficiency to the short arm of human chromosome 12. Hum. Genet. 66, 206–211 (1984).

  27. 27

    Adams, M.D., Kerlavage, A.R., Fields, C. & Venter, J.C. 3,400 new expressed sequence tags identify diversity of transcripts in human brain. Nature Genet. 4, 256–266 (1993).

  28. 28

    Cannizzaro, L.A. et al. Human homeo box-containing genes located at chromosome regions 2q31–2q37 and 12q12–12q13. Am. J. hum. Genet. 41, 1–15 (1987).

  29. 29

    Villaseca, A. Strabismus fixus. Am. J. Ophthalmol. 48, 751–762 (1959).

  30. 30

    Khodadoust, A.A. & von Noorden, G.K. Bilateral Vertical Retraction Syndrome: A Family Study. Arch. Ophthalmol. 78, 606–612 (1967).

  31. 31

    Leone, C.R. & Weinstein, G.W. Orbital fibrosis wlth enophthalmos. Ophthalmic Surg. 3, 71–75 (1972).

  32. 32

    Kunkel, L.M. et al. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc. natn. Acad. Sci. U.S.A. 74, 1245–1249 (1977).

  33. 33

    Wu, S., Seino, S. & Bell, G.I. Human collagen, type II, alpha 1, (COL2A1)gene: VNTR polymorphism detected by gene amplification. Nucl. Acids Res. 18, 3102 (1990).

  34. 34

    Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Strategies for multilocus linkage analysis in humans. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 (1984).

  35. 35

    Conneally, P.M. et al. Report of the committee on methods of linkage analysis and reporting. Cytogenet. Cell Genet. 40, 356–359 (1985).

  36. 36

    Ott, J. Analysis of Human Genetic Linkage Rev. edn. (Johns Hopkins University Press, Baltimore, 1991).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Further reading