Phenotypic and genotypic features of POC1B-associated cone dystrophy.

PURPOSE: Patients with cone dystrophy (CD) can present with virtually normal retinal appearance, which may delay diagnosis. This study describes the inconspicuous clinical features of POC1B-associated CD in two Saudi families. METHODS: This is a retrospective case study. Clinical data analyzed included multimodal retinal imaging and electroretinography of the affected individuals. Genetic analysis was done for all probands. RESULTS: Three affected males from two Saudi families with POC1B-associated CD were included. The ages at presentation ranged from 18 to 34 years. Ophthalmic examination showed decreased Snellen visual acuities (range: 20/100-20/300) and color vision bilaterally. Fundus examination showed only mild vascular attenuation. Macular optical coherence tomography showed reduced reflectivity of the external limiting membrane, ellipsoid, and interdigitation zones. Full-field electroretinography demonstrated undetectable light-adapted responses and normal dark-adapted responses in all patients. Next-generation sequencing showed one proband to be homozygous for a previously unpublished nonsense variant in POC1B (NM_172240):c.672C>G; p(Tyr224*). Whole exome sequencing for the second proband showed a novel homozygous frameshifting variant in POC1B: c.991del; p(Arg331Glufs*13). CONCLUSION: We described two novel variants in POC1B and the associated subtle, yet significant retinal features. POC1B-associated CD is a rare cause of visual loss in patients with relatively normal fundus appearance. Deep phenotyping is necessary in formulating appropriate differential diagnosis.

PRPS1-associated retinopathy: a diagnostic odyssey.

PURPOSE: This study describes how the diagnosis of Usher syndrome was revised to PRPS1-associated retinopathy and Charcot-Marie-Tooth disease type 5. CASE REPORT: A 38-year-old female with bilaterally subnormal vision and non-congenital hearing loss was initially diagnosed with Usher syndrome, based on finding variants in three genes (MYO7A, USH2A, and PCDH15), was re-evaluated at the inherited retinal disorders clinic. She had asymmetric retinopathy and right macular pseudocoloboma. She was also found to have myopathic facies, poor grip strength and atrophy of the calf muscles. Whole exome sequencing including variants in PRPS1 showed a variant (NM_002764.4:c.287 G > A; p.Arg96Gln), which was not detected by targeted Sanger sequencing of the DNA from her mother and sister. CONCLUSION: The constellation of asymmetric retinopathy and non-congenital hearing impairment should prompt the clinician to search for other diagnoses that may not be covered by an Usher syndrome next generation sequencing panel. Interpretation of genetic testing results should be correlated with a detailed clinical phenotype.