Clinical variability among patients with incomplete X-linked congenital stationary night blindness and a founder mutation in CACNA1F

Background: Incomplete X-linked congenital stationary night blindness (CSNB) is a clinically variable condition that has been shown to be caused by mutations in the calcium-channel CACNAIF gene. We assessed the clinical variability in the expression of the incomplete CSNB phenotype in a subgroup of patients of Mennonite ancestry with the same founder mutation. Methods: Sixty-six male patients from 15 families were identified with a common mutation in exon 27 of CACNAIF(L1056insC). Clinical variability in night blindness, reduced visual acuity, myopia, nystagmus and strabismus was examined. Results: At least one of the major features of CSNB (night blindness, myopia and nystagmus) was absent in 72% of the patients. All the examined features varied widely, both between and within families. Interpretation: Although the patients shared a common CACNAIF mutation, there was considerable variability in the clinical expression of the incomplete CSNB phenotype. These findings suggest the presence of other genetic factors modifying the phenotype of this disorder.