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. 1998 Apr;62(4):800–809. doi: 10.1086/301776

OA1 mutations and deletions in X-linked ocular albinism.

R E Schnur 1, M Gao 1, P A Wick 1, M Keller 1, P J Benke 1, M J Edwards 1, A W Grix 1, A Hockey 1, J H Jung 1, K K Kidd 1, M Kistenmacher 1, A V Levin 1, R A Lewis 1, M A Musarella 1, R W Nowakowski 1, S J Orlow 1, R S Pagon 1, D A Pillers 1, H H Punnett 1, G E Quinn 1, K Tezcan 1, J Wagstaff 1, R G Weleber 1
PMCID: PMC1377018  PMID: 9529334

Abstract

X-linked ocular albinism (OA1), Nettleship-Falls type, is characterized by decreased ocular pigmentation, foveal hypoplasia, nystagmus, photodysphoria, and reduced visual acuity. Affected males usually demonstrate melanin macroglobules on skin biopsy. We now report results of deletion and mutation screening of the full-length OA1 gene in 29 unrelated North American and Australian X-linked ocular albinism (OA) probands, including five with additional, nonocular phenotypic abnormalities (Schnur et al. 1994). We detected 13 intragenic gene deletions, including 3 of exon 1, 2 of exon 2, 2 of exon 4, and 6 others, which span exons 2-8. Eight new missense mutations were identified, which cluster within exons 1, 2, 3, and 6 in conserved and/or putative transmembrane domains of the protein. There was also a splice acceptor-site mutation, a nonsense mutation, a single base deletion, and a previously reported 17-bp exon 1 deletion. All patients with nonocular phenotypic abnormalities had detectable mutations. In summary, 26 (approximately 90%) of 29 probands had detectable alterations of OA1, thus confirming that OA1 is the major locus for X-linked OA.

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Selected References

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  1. Aldridge J., Kunkel L., Bruns G., Tantravahi U., Lalande M., Brewster T., Moreau E., Wilson M., Bromley W., Roderick T. A strategy to reveal high-frequency RFLPs along the human X chromosome. Am J Hum Genet. 1984 May;36(3):546–564. [PMC free article] [PubMed] [Google Scholar]
  2. Bassi M. T., Incerti B., Easty D. J., Sviderskaya E. V., Ballabio A. Cloning of the murine homolog of the ocular albinism type 1 (OA1) gene: sequence, genomic structure, and expression analysis in pigment cells. Genome Res. 1996 Sep;6(9):880–885. doi: 10.1101/gr.6.9.880. [DOI] [PubMed] [Google Scholar]
  3. Bassi M. T., Schiaffino M. V., Renieri A., De Nigris F., Galli L., Bruttini M., Gebbia M., Bergen A. A., Lewis R. A., Ballabio A. Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome. Nat Genet. 1995 May;10(1):13–19. doi: 10.1038/ng0595-13. [DOI] [PubMed] [Google Scholar]
  4. Charles S. J., Moore A. T., Grant J. W., Yates J. R. Genetic counselling in X-linked ocular albinism: clinical features of the carrier state. Eye (Lond) 1992;6(Pt 1):75–79. doi: 10.1038/eye.1992.15. [DOI] [PubMed] [Google Scholar]
  5. Creel D., O'Donnell F. E., Jr, Witkop C. J., Jr Visual system anomalies in human ocular albinos. Science. 1978 Sep 8;201(4359):931–933. doi: 10.1126/science.684419. [DOI] [PubMed] [Google Scholar]
  6. FALLS H. F. Sex-linked ocular albinism displaying typical fundus changes in the female heterozygote. Am J Ophthalmol. 1951 May;34(5 2):41–50. doi: 10.1016/0002-9394(51)90007-4. [DOI] [PubMed] [Google Scholar]
  7. Gershoni-Baruch R., Benderly A., Brandes J. M., Gilhar A. Dopa reaction test in hair bulbs of fetuses and its application to the prenatal diagnosis of albinism. J Am Acad Dermatol. 1991 Feb;24(2 Pt 1):220–222. doi: 10.1016/0190-9622(91)70030-6. [DOI] [PubMed] [Google Scholar]
  8. Holbrook K. A., Underwood R. A., Vogel A. M., Gown A. M., Kimball H. The appearance, density and distribution of melanocytes in human embryonic and fetal skin revealed by the anti-melanoma monoclonal antibody, HMB-45. Anat Embryol (Berl) 1989;180(5):443–455. doi: 10.1007/BF00305119. [DOI] [PubMed] [Google Scholar]
  9. Jaeger C., Jay B. X-linked ocular albinism: a family containing a manifesting heterozygote, and an affected male married to a female with autosomal recessive ocular albinism. Hum Genet. 1981;56(3):299–304. doi: 10.1007/BF00274683. [DOI] [PubMed] [Google Scholar]
  10. LYON M. F. Sex chromatin and gene action in the mammalian X-chromosome. Am J Hum Genet. 1962 Jun;14:135–148. [PMC free article] [PubMed] [Google Scholar]
  11. Nakagawa H., Hori Y., Sato S., Fitzpatrick T. B., Martuza R. L. The nature and origin of the melanin macroglobule. J Invest Dermatol. 1984 Aug;83(2):134–139. doi: 10.1111/1523-1747.ep12263325. [DOI] [PubMed] [Google Scholar]
  12. Nathans J., Piantanida T. P., Eddy R. L., Shows T. B., Hogness D. S. Molecular genetics of inherited variation in human color vision. Science. 1986 Apr 11;232(4747):203–210. doi: 10.1126/science.3485310. [DOI] [PubMed] [Google Scholar]
  13. Newton J. M., Orlow S. J., Barsh G. S. Isolation and characterization of a mouse homolog of the X-linked ocular albinism (OA1) gene. Genomics. 1996 Oct 15;37(2):219–225. doi: 10.1006/geno.1996.0545. [DOI] [PubMed] [Google Scholar]
  14. O'Donnell F. E., Green W. R., McKusick V. A., Forsius H., Eriksson A. W. Forsius-Eriksson syndrome: its relation to the Nettleship-Falls X-linked ocular albinism. Clin Genet. 1980 Jun;17(6):403–408. doi: 10.1111/j.1399-0004.1980.tb00170.x. [DOI] [PubMed] [Google Scholar]
  15. O'Donnell F. E., Jr, Green W. R., Fleischman J. A., Hambrick G. W. X-linked ocular albinism in Blacks. Ocular albinism cum pigmento. Arch Ophthalmol. 1978 Jul;96(7):1189–1192. doi: 10.1001/archopht.1978.03910060023005. [DOI] [PubMed] [Google Scholar]
  16. O'Donnell F. E., Jr, Hambrick G. W., Jr, Green W. R., Iliff W. J., Stone D. L. X-linked ocular albinism. An oculocutaneous macromelanosomal disorder. Arch Ophthalmol. 1976 Nov;94(11):1883–1892. doi: 10.1001/archopht.1976.03910040593001. [DOI] [PubMed] [Google Scholar]
  17. O'Donnell F. E., Jr, King R. A., Green W. R., Witkop C. J., Jr Autosomal recessively inherited ocular albinism. A new form of ocular albinism affecting females as severely as males. Arch Ophthalmol. 1978 Sep;96(9):1621–1625. doi: 10.1001/archopht.1978.03910060255013. [DOI] [PubMed] [Google Scholar]
  18. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  19. Pearce W. G., Johnson G. J., Gillan J. G. Nystagmus in a female carrier of ocular albinism. J Med Genet. 1972 Mar;9(1):126–129. doi: 10.1136/jmg.9.1.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reichel M., Grix A. C., Isseroff R. R. Dyskeratosis congenita associated with elevated fetal hemoglobin, X-linked ocular albinism, and juvenile-onset diabetes mellitus. Pediatr Dermatol. 1992 Jun;9(2):103–106. doi: 10.1111/j.1525-1470.1992.tb01223.x. [DOI] [PubMed] [Google Scholar]
  21. Russell-Eggitt I., Kriss A., Taylor D. S. Albinism in childhood: a flash VEP and ERG study. Br J Ophthalmol. 1990 Mar;74(3):136–140. doi: 10.1136/bjo.74.3.136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schiaffino M. V., Bassi M. T., Galli L., Renieri A., Bruttini M., De Nigris F., Bergen A. A., Charles S. J., Yates J. R., Meindl A. Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism. Hum Mol Genet. 1995 Dec;4(12):2319–2325. doi: 10.1093/hmg/4.12.2319. [DOI] [PubMed] [Google Scholar]
  23. Schnur R. E., Knowlton R. G., Musarella M. A., Muenke M., Nussbaum R. L. Partial deletions of a sequence family ("DXS278") and its physical linkage to steroid sulfatase as detected by pulsed-field gel electrophoresis. Genomics. 1990 Oct;8(2):255–262. doi: 10.1016/0888-7543(90)90280-8. [DOI] [PubMed] [Google Scholar]
  24. Schnur R. E., Nussbaum R. L., Anson-Cartwright L., McDowell C., Worton R. G., Musarella M. A. Linkage analysis in X-linked ocular albinism. Genomics. 1991 Apr;9(4):605–613. doi: 10.1016/0888-7543(91)90353-g. [DOI] [PubMed] [Google Scholar]
  25. Schnur R. E., Trask B. J., van den Engh G., Punnett H. H., Kistenmacher M., Tomeo M. A., Naids R. E., Nussbaum R. L. An Xp22 microdeletion associated with ocular albinism and ichthyosis: approximation of breakpoints and estimation of deletion size by using cloned DNA probes and flow cytometry. Am J Hum Genet. 1989 Nov;45(5):706–720. [PMC free article] [PubMed] [Google Scholar]
  26. Schnur R. E., Wick P. A., Bailey C., Rebbeck T., Weleber R. G., Wagstaff J., Grix A. W., Pagon R. A., Hockey A., Edwards M. J. Phenotypic variability in X-linked ocular albinism: relationship to linkage genotypes. Am J Hum Genet. 1994 Sep;55(3):484–496. [PMC free article] [PubMed] [Google Scholar]
  27. Schnur R. E., Wick P. A., Sosnoski D. N., Bick D., Nussbaum R. L. Deletion mapping and a highly reduced radiation hybrid in the Xp22.3-p22.2 region. Genomics. 1993 Mar;15(3):500–506. doi: 10.1006/geno.1993.1100. [DOI] [PubMed] [Google Scholar]

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