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Anat Blumenfeld, Sandra Feder Hevroni, Efrat Shemesh, Dalia Eli, Irene Anteby, Ada Rosenmann, Claudia Yahalom; A P Gene Mutation (OCA2) Causing Various Phenotypes. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1562.
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© ARVO (1962-2015); The Authors (2016-present)
Mild phenotypes of Oculocutaneous Albinism type 2 (OCA2) were described in compound heterozygotes for the P mutation A481T. Our accumulated data indicate that the phenotype of compound heterozygote albinos is determined by the "mild mutation". Transfection of null melanocytes with T481 cDNA restored approximately 70% of their function as compared to wild-type A481 cDNA.Our purpose was to determine the phenotypic range of albinism caused by A481T in Jewish albinos.
Phenotypic evaluation included hair, eye and skin color, presence of nevi and ability to tan. Eye examination included visual acuity, photophobia, presence of nystagmus, transillumination, visibility of choroidal vessels and hypoplasia of the macula. Blood DNA was PCR amplified followed by restriction digest or sequencing.
Four OCA2 and 3 normal offspring of phenotypically normal parents were studied. Two siblings were homozygotes for the G27R mutation in P and two were compound heterozygotes for G27R and A481T. The mother was a carrier of G27R while the father and a baby were compound heterozygotes for G27R and A481T, but differed dramatically from the two compound heterozygote OCA2 siblings: they had normal pigmentation and almost no ocular signs. To determine if P mutations were the cause of albinism in the two compound heterozygote OCA2 siblings we sequenced TYR, TYRP1, SLC45A2 and GPR143, causing OCA1, OCA3, OCA4 and X-linked Ocular albinism (OA), but no mutation was identified. Hence, G27R and A481T were the only identified mutations in this family. We further screened the cohort of Israeli Jewish albinos and identified one homozygote and 14 additional heterozygotes for A481T, all exhibiting mild phenotypes with the differential diagnosis of OCA, OA, congenital nystagmus or normal. The second P mutation was identified in part of these 14 albinos. None of 130 unrelated, normally pigmented Israeli Jewish individuals carried the A481T mutation.We also detected normal to very mild phenotypes of albinism in compound heterozygotes for "severe" and "very mild" TYR mutations: R217W, P406L and R402Q.
In Caucasians the P mutation A481T causes normal phenotype to very mild albinism with inter- and intra-familial variability. The same phenomenon was detected in compound heterozygotes for "severe" and "very mild" TYR mutations. The question remains what is the relevance of two identified TYR or P mutations in normal individuals.
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