ClinVar

In a 4-year-old boy of northern European ancestry with typical type II oculocutaneous albinism (OCA2; 203200), Lee et al. (1994) identified compound heterozygosity for 2 mutations in the OCA2 gene: a G-to-A transition, resulting in a val443-to-ile (V443I) substitution inherited from the mother, and a C-to-T transition in exon 22 resulting in a pro743-to-leu (P743L; 611409.0005) substitution inherited from the father. The patient's skin was very lightly pigmented with no apparent tanning ability, and his hair was pale golden yellow. His irides were blue and showed transillumination, and the fundi appeared nonpigmented, with hypoplastic maculae. His corrected visual acuity was 20/100, and he had nystagmus and strabismus. Chromosomal analysis demonstrated mosaicism for 46,XY and 46,XY,dup(15)(q12). The duplication, which occurred in 25% of stimulated peripheral-blood leukocytes, was interpreted as a nonpathologic chromosomal variant (Ludowese et al., 1991). Lee et al. (1994) found the same V443I substitution on the maternally derived chromosome 15 in a 7-year-old boy with typical type II oculocutaneous albinism and Prader-Willi syndrome (PWS; 176270), the latter being due to deletion of 15q11.2-q13.1 derived from the father. The paternal OCA2 gene was deleted in this child.

In a mother and 3 of her children in a Czech family with oculocutaneous or ocular albinism, Jedlickova et al. (2023) identified homozygosity or compound heterozygosity for the V443I mutation in the OCA2 gene. The mother and a daughter, who both had oculocutaneous albinism, were compound heterozygous for V443I and a large complex rearrangement in the OCA2 gene, whereas the 2 sons, who had ocular albinism, were homozygous for the V443I substitution. The authors noted that the sons had normal visual acuity with discrete fundus hypopigmentation and foveal hypoplasia, which was only revealed due to the familial investigation; they suggested that these findings supported the notion of V443I as a hypomorphic allele causing only a partial loss of function, thus accounting for the 4 homozygous individuals present in the gnomAD database (v2.1.1).