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Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype

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Abstract

Oculocutaneous albinism (OCA) is a common human genetic condition resulting from mutations in at least twelve different genes. OCA1 results from mutations of the tyrosinase gene and presents with the life-long absence of melanin pigment after birth (OCA1A) or with the development of minimal-to-moderate amounts of cutaneous and ocular pigment (OCA1B). Other types of OCA have variable amounts of cutaneous and ocular pigment. We hypothesized that white hair at birth indicates OCA1 and tested this in a sample of 120 probands with OCA and white hair at birth. We found that 102 (85%) of the probands had OCA1 with one or two identifiable tyrosinase gene mutations, with 169 (83%) of the 204 OCA1 tyrosinase gene alleles having identifiable mutations and 35 (17%) having no identifiable change in the coding, splice junction, or proximal promoter regions of the gene. The inability to identify the mutation was more common with OCA1B (24/35, 69%) than with OCA1A (11/35, 31%) alleles. Seven probands with no tyrosinase gene mutations were found to have OCA2 with one or two P gene mutations, and in eleven, no mutations were detected in either gene. We conclude that (1) the presence of white hair at birth is a useful clinical tool suggesting OCA1 in a child or adult with OCA, although OCA2 may also have this presentation; (2) the molecular analysis of the tyrosinase and P genes are necessary for precise diagnosis; and (3) the presence of alleles without identifiable mutations of the tyrosinase gene, particularly in OCA1B, suggests that more complex mutation mechanisms of this gene are common in OCA.

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Acknowledgements

The authors thank the wonderful families who have participated in this research and the many physicians who have referred the families to the International Albinism Center. This research was supported in part by United States Public Health grant AR44649 and by the Bernard and Mary Ellen Black family.

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Authors and Affiliations

  1. Department of Medicine, University of Minnesota, Minneapolis, Minn., USA

    Richard A. King, Jacy Pietsch, James P. Fryer, Sarah Savage, Marcia J. Brott & William S. Oetting

  2. Department of Ophthalmology, University of Minnesota, Minneapolis, Minn., USA

    C. Gail Summers

  3. Department of Pediatrics, University of Minnesota, Minneapolis, Minn., USA

    C. Gail Summers

  4. Institute of Human Genetics, University of Minnesota, Minneapolis, Minn., USA

    Richard A. King, Jacy Pietsch, James P. Fryer, Sarah Savage, Marcia J. Brott & William S. Oetting

  5. Great Ormond Street Hospital for Children, London, UK

    Isabelle Russell-Eggitt

  6. MMC 485, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA

    Richard A. King

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  1. Richard A. King
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  2. Jacy Pietsch
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  7. C. Gail Summers
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Correspondence to Richard A. King.

Additional information

Electronic database Information: accession numbers and URLs for data presented in this article are as follows:

Albinism Database, http://www.cbc.umn.edu/tad, for a list of published mutations of the tyrosinase gene

Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/, for OCA1 (MIM 203100), OCA2 (MIM 203200)

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King, R.A., Pietsch, J., Fryer, J.P. et al. Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype. Hum Genet 113, 502–513 (2003). https://doi.org/10.1007/s00439-003-0998-1

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