An OTX2 Gene Mutation Causing a More Severe Retinal Phenotype in a Female RPGR Mutation Carrier

This study describes the clinical features of a pedigree with a novel retinitis pigmentosa GTPase regulator gene mutation in whom one hemizygous man has a typical manifesting phenotype and three heterozygous women demonstrate a typical carrier phenotype. A fourth heterozygous woman is described with a strikingly severe retinal phenotype and also harbors an independent disease-causing mutation in the OTX2 gene and an associated systemic phenotype. This study hypothesizes that the OTX2 mutation in combination with the familial retinitis pigmentosa GTPase regulator gene variant results in a more severe ocular phenotype than is seen in the other heterozygous women in this pedigree due to a loss of OTX2-mediated photoreceptor protection.