Clinical and molecular characterization of a family affected with X-linked ocular albinism (OA1)

Thirty-one members of a family affected with X-linked ocular albinism (OA1) were studied to characterize the clinical phenotype and identify the disease-causing mutation. The family members were examined with ophthalmoscopy, electroretinography, and Goldmann perimetry. Linkage analysis was performed with markers from the OA1 locus. Exons 2 and 8 of the OA1 gene were assayed with the polymerase chain reaction (PCR). The six affected males had visual acuities ranging from 20/40 to 20/200. All had nystagmus, iris transillumination, and foveal hypoplasia. The eldest affected male had 20/40 vision and was asymptomatic. The level of the visual acuity of the affected males was not related to the degree of retinal pigmentation. All seven female carriers had normal visual function but were found to have iris transillumination defects and variable retinal pigmentary appearance ranging from minimal pigmentary disturbance, patchy and diffuse hypopigmentation, to classic 'mud-splattered' appearance. Linkage analysis was consistent with a disease-causing mutation at the OA1 locus. PCR analysis revealed a deletion which includes at least the portion of the OA1 gene between exons 2 and 8. Affected males with X-linked ocular albinism can have a visual disability that ranges from almost none to legal blindness, and the female carriers can have variable retinal pigmentary appearance. Mutation screening of the OA1 gene can be used to confirm the diagnosis in isolated males of some families, and genetic linkage analysis can be used to accurately identify carriers even when the specific mutation cannot be identified.