Background: To present the ophthalmological findings of a mother and son initially diagnosed with benign concentric annular macular dystrophy (BCAMD) and later discovered to carry a novel nonsense mutation in the cone-rod homeobox (CRX) gene (19q13.3).
Materials and methods: Patients received ophthalmic examinations and diagnostic testing. The proband underwent sequencing of 131 retinal dystrophy genes. His mother had targeted testing of the identified sequence variations in CRX and BBS12 (4q27).
Results: The proband (Case I) presented at age 35 years for routine care. He had several male and female relatives with adult-onset retinal degeneration. Over 11 years, visual acuity (VA) dropped from 20/20 OU to 20/25 OD and 20/50 OS. Ophthalmoscopy showed bull's eye macular lesions OU. The proband's mother (Case II) presented at age 57 years with unilateral, progressive vision loss. Over 5 years, VA fluctuated 20/80-20/400 OD and remained 20/25 OS. Ophthalmoscopy showed similar findings to Case I. A clinical diagnosis of BCAMD was given because of the characteristic retinal lesion, preserved VA, and presumed autosomal dominant inheritance. Genetic testing identified a novel nonsense mutation in CRX (c.766C>T; p.Gln256Ter) in both patients. The son was also heterozygous for a missense mutation in BBS12 (c.1859A>G; p.Gln620Arg), which was absent in Case II.
Conclusions: CRX mutations are associated with a variety of clinical phenotypes, including an adult-onset macular dystrophy that simulates BCAMD with a bull's eye macular lesion and fairly well preserved VA.
Keywords: CRX mutation; Retinal dystrophy; benign concentric macular dystrophy; bull’s eye maculopathy; cone-rod homeobox gene.