gms | German Medical Science

Mutations in CACNA1F have been associated with the phenotypes of X-linked congenital stationary night blindness type 2A (CSNB2A), Åland Island Eye disease (ÅIED) and X-linked cone-rod dystrophy (CORDX3). We report a large family of German origin carrying a novel CACNA1F deletion. The phenotype included features of CSNB2A / ÅIED and CORDX3. A complete ophthalmologic examination in four affected males (aged 3, 8, 51 and 73 years) and two female conductors (aged 43 and 45 years) comprised best corrected visual acuity, colour vision, visual fields, biomicroscopy, fundus examination, fundus photography, optic coherence tomography (OCT), electroretinography (ERG) and an orthoptic examination. Genetic analysis was carried out using a combined linkage and targeted X-chromosomal next generation sequencing approach. Clinically, all four males showed severely reduced visual acuity of 0.2 (20/100) or less. All patients were myopic (range –3.75 to –23.0 D) with older patients requiring higher corrections. Colour vision was defective in the three patients tested. Two patients displayed strabismus. The two boys showed discreet pallor of the optic nerve head and discreet irregular pigmentation in the macular area, the two adults had myopic fundus changes. Three of the four patients had congenital nystagmus. OCT examination in the two boys revealed a normal foveal configuration. Due to nystagmus and staphylomata, OCT in the two adults showed artefacts. Full-field electroretinogram could be recorded in three of the four patients and was abnormal. The school boy showed reduced scotopic a- and b-waves with photopic answers below noise level. In the two adults, scotopic a- and b-waves were severely reduced with non-recordable photopic ERG. This indicates a severe, diffuse retinal loss of function. The female carriers were asymptomatic. Genetic analysis revealed a novel gross 4453 bp (in-frame loss of 801 bp on cDNA level) deletion encompassing exons 18 to 26 of the CACNA1F gene. The mutation completely segregated with disease phenotype (males) respectively carrier status (females) in the family. Conclusions: The described novel CACNA1F deletion causes a severe phenotype with overlapping clinical features of CSNBX2/ÅIED and CORDX3, illustrating the highly variable phenotypic spectrum associated with CACNA1F mutations.