Identification of a novel CACNA1F mutation in a Chinese family with CORDX3

BACKGROUND: X‐linked cone‐rod dystrophy (CORDX) is one form of inherited retinal disorders (IRDs) characterized by progressive dysfunction of photoreceptor. Three types of CORDX were reported and CACNA1F gene defect can cause CORDX3. The aim of this study was to investigate the pathogenic variant in a Chinese family with IRD. METHODS: The two affected subjects including the proband and his elder sister underwent ophthalmic examinations. Whole exome sequencing (WES) was performed in the proband at first, then co‐segregation analysis was performed in the family by Sanger sequencing. Minigene approach was used to verify the effect of the mutation on the splicing of CACNA1F. X‐chromosomal inactivation assay was performed to evaluate the inactivation patterns of the female carriers. RESULTS: The ophthalmic examination results of the proband fit the clinical description of CORDX3, and the female patient presented with only mild symptoms due to mildly skewed X‐chromosomal inactivation (ratio 67: 33). Molecular genetic testing identified a novel splice‐site mutation c.3847‐2A > G in CACNA1F (NM_005183.4) gene in the patients, which inherited from their asymptomatic mother. Minigene approach confirmed that c.3847‐2A > G could affect the splicing of CACNA1F. CONCLUSION: Our study identified a novel splice‐site mutation in the CACNA1F gene, which expanded the mutational spectrum of CACNA1F‐releated diseases and demonstrated the importance of combining clinical and genetic testing in the diagnosis of IRDs.