Article | Published:

Autosomal recessive ocular albinism associated with a functionally significant tyrosinase gene polymorphism

Abstract

Autosomal recessive ocular albinism (AROA) is a disorder characterized by reduced pigmentation of the retina and iris, hypoplastic fovea, variably reduced visual acuity and nystagmus. Pigmentation of the skin and hair is normal, but is usually slightly lighter than in unaffected sibs. We analysed 12 unrelated patients with AROA, and found that two had abnormalities of the tyrosinase (TYR) gene. These two patients were each a compound heterozygote for a different pathologic mutant allele and an allele containing a ‘normal’ polymorphism, Arg402Gln, which results in a tyrosinase polypeptide with reduced thermal stability. In these patients, AROA thus appears to represent a clinically mild form of OCA1, with a fixed visual deficit resulting from low tyrosinase activity during fetal development but with normal pigmentation of the skin and hair postnatally.

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

    Sprite, R.A. Molecular genetics of oculocutaneous albinism. Sem. Dermatol. 12, 167–172 (1993).

  2. 2

    Sprite, R.A. Molecular genetics of oculocutaneous albinism. Hum. molec. Genet. 3, 1469–1475 (1994).

  3. 3

    Sprite, R.A. & Hearing, V.J., Genetic disorders of pigmentation. Adv. hum. Genet. 22, 1–45 (1995).

  4. 4

    Lee, S.-T. et al. Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism. New Engl. J. Med. 330, 529–534 (1994).

  5. 5

    Lee, S.-T. et al. Diverse mutations of the P gene among African-Americans with type II (tyrosinase-positive) oculocutaneous albinism (OCA2). Hum. molec. Genet. 3, 2047–2051 (1994).

  6. 6

    Tripathi, R.K., Giebel, L.B., Strunk, K.M. & Spritz, R.A. A polymorphism of the human tyrosinase gene is associated with temperature-sensitive enzymatic activity. Gene Exp. 1, 103–110 (1991).

  7. 7

    Giebel, L.B., Strunk, K.M. & Sprite, R.A. Organization and nucleotide sequences of the human tyrosinase gene and a truncated tyrosinase-related segment. Genomics 9, 435–445 (1991).

  8. 8

    Lee, S.-T., Nicholls, R.D., Jong, M.T.C. & Spritz, R.A. Organization and sequence of the human P gene and identification of a new family of transport proteins. Genomics(in the press).

  9. 9

    Spritz, R.A. et al. Mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene account for a continuous range of phenotypes in human plebaldim. Am. J. hum. Genet. 51, 1058–1065 (1992).

  10. 10

    King, R.A., Mentink, M.M. & Oetting, W.S. Non-random distribution of missense mutations within the human tyrosinase gene in type I (tyrosinase-reiated) oculocutaneous albinism. Molec. Biol. Med. 8, 19–29 (1991).

  11. 11

    Piratsu, M., Saglio, G., Chang, J.C., Cao, A. & Kan, Y.W. Initiation codon mutation as a cause of alpha-thalassemia. J. biol. Chem. 259, 12315–12317 (1984).

  12. 12

    Moi, P., Cash, F.E., Liebhaber, S.A., Cao, A. & Piratsu, M. An initiation codon mutation (AUG-to-GUG) of the human alpha-1-globin gene: structural characterization and evidence for a mild thalassemic phenotype. J. clin. Invest. 80, 1416–1421 (1987).

  13. 13

    Saba, L. et al. A novel beta-thalassemia mutation (G-to-A) at the Initiation codon of the beta-globin gene. Hum. Mut. 1, 420–422 (1992).

  14. 14

    Beris, P., Darbellay, R., Speiser, D., Kirchner, V. & Miescher, P. De novo Initiation codon mutation (ATG-to-ACG) of the beta-globin gene causing beta-thalassemia in a Swiss family. Am. J. Hematol. 42, 248–253 (1993).

  15. 15

    Giebel, L.B. & Sprite, R.A. RFLP for Mbol In the human tyrosinase (TYR) gene detected by PCR. Nucl. Acids Res. 18, 3103 (1990).

  16. 16

    Tripathi, R.K. et al. Mutations of the tyrosinase gene in Indo-Pakistani patients with type I (tyrosinase-deficient) oculocutaneous albinism (OCA). Am. J. hum. Genet. 53, 1173–1179 (1993).

  17. 17

    Giebel, L.B. et al. Tyrosinase gene mutations associated with type IB (“yellow”) oculocutaneous albinism. Am. J. hum. Genet. 48, 1159–1167 (1991).

  18. 18

    Tripathi, R.K., Hearing, V.J., Urabe, K., Aroca, P. & Spritz, R.A. Mutational mapping of the catalytic activities of human tyrosinase. J. biol. Chem. 267, 23707–23712 (1992).

  19. 19

    Clapp III, J.F. Changing thermal response to endurance exercise during pregnancy. Am. J. Obstetr. Gynecol. 165, 1684–1689 (1991).

  20. 20

    Alloisio, N. et al. Spαv/41: a common spectrin polymorphism at the IV-V domain junction. J. clin. Invest. 87, 2169–2177 (1991).

  21. 21

    Witkop Jr., C.J., Quevedo, W.C., Fitzpatrick, T.B. & King, R.A. in The metabolic basis of Inherited disease. 6th edn (eds Scriver, C. R et al.). 2905–2947 (McGraw-Hill, New York, 1989).

  22. 22

    Apkarian, P. & Shallo-Hofmann, J. VEP projections in congenital nystagmus; VEP asymmetry in albinism: a comparison study. Investig. Ophthalm. Vis. Sci. 32, 2653–2661 (1991).

  23. 23

    Apkarian, P. A practical approach to albino diagnosis. Ophthalm. Pediatr. Genet. 13, 77–88 (1992).

  24. 24

    Giebel, L.B., Musarella, M.A. & Spritz, R.A. A nonsense mutation In the tyrosinase gene of Afghan patients with tyrosinase negative (type IA) oculocutaneous albinism. J. med. Genet. 28, 464–467 (1991).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Further reading