Abstract
Oculocutaneous albinism type 2 (OCA2) is a human autosomal-recessive hypopigmentation disorder associated with pathological mutations of the OCA2 gene. In this study, we investigated a form of OCA in a Polynesian population with an observed phenotype characterized by fair skin, some brown nevi present in the sun-exposed areas and green or blue eyes. Hair presented with a unique red coloration since birth, with tones ranging across individuals from Yellow-Red to Brown-Red, or Auburn. We genetically screened for mutations in the OCA2 and MC1R genes as their products have previously been shown to be associated with red hair/fair skin and OCA2. The SLC45A2 gene was also screened to identify any possible relation to skin color variation. We have identified a novel missense substitution in the OCA2 gene (Gly775Asp) responsible for OCA2 in individuals of Polynesian heritage from Tuvalu. The estimated incidence of this form of OCA2 in the primary study community is believed to occur at one of the highest recorded rates of albinism at approximately 1 per 669 individuals. In addition, we have analyzed four unrelated individuals with albinism who have Polynesian heritage from three other separate communities and found they carry the same OCA2 mutation. We also analyzed an out-group comprising three unrelated individuals with albinism of Melanesian ancestries from two separate communities, one Australian Aboriginal and three Australian Caucasians, and did not detect this mutation. We hypothesize that this mutation may be Polynesian specific and that it originated from a common founder.
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Acknowledgements
We thank all the individuals who participated in this study. For the collection of samples, assistance from the Princess Margaret Hospital and the Red Cross Organization of Tuvalu is greatly appreciated. We thank Dr Jennifer Kromberg from Queensland Clinical Genetics Service for her advice on the study, the referral of potential melanesian participants and inclusion of the Australian Aboriginal sample. We are grateful to the dermatologist Professor Ross Barnetson of the Sydney Cancer Centre and Lisa McMurray, Program Director for the International Centre for Eye Education (ICEE), UNSW Sydney and the NSW & RACS PIP ophthalmology team, for their cooperation during this study. The OCA2 microsatellite used as a marker for inheritance in this study was generously provided by Professor Michele Ramsay, NHLS South Africa. We also thank Dr Val Hyland of the Neonatal Screening Unit, Royal Brisbane Hospital for assistance with laboratory techniques. Darren Smit and Wen Lim for help in classifying the phenotype and genotypes of participants. Panapa Patiale and Sunema Makatui for their work as Tuvaluan interpreters and for introducing the researcher to potential participants. Jeff Malua for his work in translating all participant research documents from English to Tuvaluan language. Siemai Patiale for her assistance as in-Country liaison. HCJ was supported by an Institute for Molecular Bioscience postgraduate scholarship to conduct this work. CW and RAS are both Senior Research Fellows of the Australian NHMRC.
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Johanson, H., Chen, W., Wicking, C. et al. Inheritance of a novel mutated allele of the OCA2 gene associated with high incidence of oculocutaneous albinism in a Polynesian community. J Hum Genet 55, 103–111 (2010). https://doi.org/10.1038/jhg.2009.130
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DOI: https://doi.org/10.1038/jhg.2009.130
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