Purpose: We investigated the genetic characteristics of retinitis pigmentosa 1-like 1 (RP1L1) gene in patients with occult macular dystrophy (OMD) and identified genotype-phenotype correlations.
Methods: We sequenced the entire exons and flanking regions of the RP1L1 gene in 19 Korean OMD patients. Detailed retinal morphologic abnormalities were evaluated using spectral domain optical coherence tomography and infrared reflectance imaging. Clinical features, retinal morphologic abnormalities, and disease progression were compared among the subtypes separated on the basis of genotypes.
Results: Ten of 19 (52.6%) patients had RP1L1 mutations: 7 (36.8%) had the previously reported mutation, p.Arg45Trp, and the other 3 (15.8%) had novel variants (p.Gln2311Pro, p.Ser676Cys, and p.Asp1425His). p.Gln2311Pro, p.Asp1425His, and p.Ser676Cys were predicted as pathogenic in 3, 2, and none of 5 computational assessment tools, respectively. Photoreceptor disruption across the fovea was symmetric in all eyes with RP1L1 mutations, but asymmetric in 3 eyes without the mutations. Symmetric round hyporeflectance centered on the fovea in infrared reflectance images was seen in all patients with the p.Arg45Trp mutation, but in only 2 of 12 patients without the mutation. The patients with p.Arg45Trp showed greater extent of photoreceptor disruption than those without the mutation. Progression of photoreceptor disruption was remarkable in patients with RP1L1 mutations, but insignificant in those without.
Conclusions: OMD is clinically and genetically heterogeneous, with different morphologic features and progression in outer retinal pathology according to RP1L1 gene mutations, indicating the genotype-phenotype correlation in patients with OMD.
Keywords: RP1L1; genotype; occult macular dystrophy; optical coherence tomography; phenotype.