CRB1 related retinal degeneration with novel mutation

PURPOSE: To describe novel and previously unreported genetic mutations in the CRB1 gene in a patient with retinal dystrophy. To increase the genotype-phenotype understanding of CRB1-related retinal degenerative diseases and describe patients’ response to therapy. OBSERVATIONS: Patient was evaluated for progressive loss of central and peripheral vision. Fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FA), and ocular-coherence tomography (OCT) were used in the evaluation. Genetic screening was performed to explore underlying mutations. Genetics revealed a previously reported, pathogenic variant in the CRB1 gene (c.2842+5G > A), and a novel mutation (c.4014T > A) whose clinical significance is uncertain due to the absence of conclusive evidence. This case is phenotypically unique in that CME was refractory to therapy, while CME in CRB1 related maculopathy typically responds well to treatment. CONCLUSIONS AND IMPORTANCE: This study adds a breadth of phenotypic understanding to genetic analysis in CRB1 related retinal degenerative conditions. The newly described CRB1 variant mutation c.4014T > A may portend a poor prognosis for CME responsiveness to therapy. Genetic testing in an otherwise unexplained CME event may be useful to identify underlying CRB1 variants and reveal genotype-phenotype correlations, which may alter the treatment plan and prognosis.