A comprehensive genetic study of autosomal recessive ocular albinism in Caucasian patients.

PURPOSE: Autosomal recessive ocular albinism (AROA) is a group of genetic disorders in which reduced pigmentation of the eye is associated with decreased visual acuity, nystagmus, strabismus, and photophobia, although pigmentation of skin and hair is relatively normal. Previous studies have shown that AROA in some cases constitutes a clinically mild presentation of oculocutaneous albinism (OCA), due to mutations in either the TYR (OCA1) or OCA2 (P) genes. The purpose of this study was to characterize the relative prevalence of different genetic forms of AROA, and to characterize a sample repertoire of gene mutations in a large series of Caucasian patients with AROA.

METHODS: Thirty-six unrelated Caucasian patients carrying the clinical diagnosis of AROA were studied by DNA sequence analysis of the four classic OCA genes: TYR, OCA2 (P), TYRP1, and SLC45A2 (MATP), as appropriate. In all patients with no apparent pathologic mutations in these genes, DNA sequence analysis was performed of a candidate OCA gene, SILV, and the two genes most often involved in Hermansky-Pudlak syndrome, HPS1 and HPS4, the most frequent syndromic form of OCA.

RESULTS: TYR gene mutations were identified in 20 (56%) patients, OCA2 mutations in 3 (8%), mutations in both TYR and OCA2 in 2 (6%), and possible TYRP1 mutations in 2 (6%). In at least nine patients, no mutations were found in any of the genes studied. Almost all patients with OCA1-related AROA were compound heterozygous for severe OCA1 mutant alleles and the common R402Q variant.

CONCLUSIONS: Most patients with AROA represent phenotypically mild variants of OCA, well over half of which is OCA1.