Fundus albipunctatus and retinitis punctata albescens in a pedigree with an R150Q mutation in RLBP1

Fundus albipunctatus (FA; OMIM 136880) is a rare form of apparently station ary night blindness characterized by the presence of myriad symmetrical rou nd white dots in the fundus with a greater concentration in the midperipher y. A distantly similar but distinct clinical entity, retinitis punctata alb escens (RPA), is also characterized by aggregation of irregular white fleck s but is progressive and evolves to generalized atrophy of the retina. We s tudied 4 consanguineous kindreds diagnosed with FA from Saudi Arabia. Given the substantial phenotypic variation and overlap between different flecked retinal dystrophies, we evaluated all known genes associated with such con ditions by both genetic analysis and direct sequencing. In one kindred, KKE SH-099, we identified a homozygous R150Q alteration in RLBP1, the gene enco ding the cellular retinaldehyde binding protein, associated previously with both recessive retinitis pigmentosa (arRP) and RPA. Examination of several patients aged 3-20 years over a 9-year period presented no evidence for ei ther RP or RPA. In contrast, clinical examination of individuals with the s ame mutation in their fourth and fifth decade revealed signs consistent wit h RPA. The data suggest that the R150Q mutation in RLBP1 may result in RPA with slow progression. More importantly, younger individuals diagnosed with the milder disorder FA thought to be stationary may evolve to a more devas tating and progressive phenotype.