A Novel Splice-Site Variant in CACNA1F Causes a Phenotype Synonymous with Åland Island Eye Disease and Incomplete Congenital Stationary Night Blindness

Background: CACNA1F-related disorders encompass progressive and non-progressive disorders, including angstrom land island eye disease and incomplete congenital stationary night blindness. These two X-linked disorders are characterized by nystagmus, color vision defect, myopia, and electroretinography (ERG) abnormalities. Ocular hypopigmentation and iris transillumination are reported only in patients with angstrom land island eye disease. Around 260 variants were reported to be associated with these two non-progressive disorders, with 19 specific to angstrom land island eye disease and 14 associated with both angstrom land island eye disease and incomplete congenital stationary night blindness. CACNA1F variants spread on the gene and further analysis are needed to reveal phenotype-genotype correlation. Case Report: A complete ocular exam and genetic testing were performed on a 13-year-old boy. A novel splice-site variant, c.4294-11C>G in intron 36 in CACNA1F, was identified at hemizygous state in the patient and at heterozygous state in his asymptomatic mother and explained the phenotype synonymous with angstrom land island eye disease and incomplete congenital stationary night blindness observed in the patient. Conclusion: We present a novel variant in the CACNA1F gene causing phenotypic and electrophysiologic findings indistinguishable from those of AIED/CSNB2A disease. This finding further expands the mutational spectrum and our knowledge of CACNA1F-related disease.

Automated summary

CACNA1F-related disorders consist of progressive and non-progressive conditions, including Angstrom Land Island eye disease and incomplete congenital stationary night blindness. A novel splice-site variant in the CACNA1F gene was identified in a 13-year-old boy, leading to phenotypic similarities with Angstrom Land Island eye disease and incomplete congenital stationary night blindness. This finding expands our understanding of CACNA1F-related diseases.