Abstract
BACKGROUND Ocular coloboma is a rare congenital malformation of the optic fissure. Previous literature has indicated that pathogenic changes in the RARB gene are associated with syndromic ocular coloboma, specifically pulmonary hypoplasia/agenesis, diaphragmatic hernia/eventration, anophthalmia/microphthalmia, and cardiac defect (PDAC) syndrome. There are limited reports of non-syndromic cases of ocular coloboma associated with pathogenic variants in the RARB gene. CASE REPORT We report a mother and son with isolated ocular coloboma and identify a novel variant of uncertain significance in the RARB gene that is potentially pathogenic for ocular coloboma. The proband was a 6-month-old male infant with colobomas in the right retina as well as the left retina, iris, and optic nerve. His mother had right eye iris and retinal coloboma. Chromosomal microarray analysis detected a 36 kb deletion within exon 2 of the RARB gene that was confirmed by next-generation sequencing to be present in the mother and absent in the asymptomatic father. CONCLUSIONS Our study reports a maternally inherited deletion in exon 2 of the RARB gene associated with familial isolated coloboma. This novel variant provides new knowledge of the gene-disease spectrum of RARB. Further research is needed to better understand the role of the RARB gene in the pathogenesis of non-syndromic coloboma.