A mutation in CACNA1F gene found by Whole Exome Sequencing (WES) and in silico analysis in an Iranian family with consanguineous relationships

During a premarital study of a family-related couple, some exonic mutations in different genes under autosomal recessive and X-linked genetic inheritances were observed in the female case. After genetic counseling, DNA was extracted from the blood of the men and women, and then the Whole Exome Sequencing (WES) technique was used to look for possible pathogenic mutations in the two individuals. Also, after drawing the couple's pedigree, candidate mutations were examined in the woman's parents as well as her uncles. For further investigations, in silico analyses were performed through SWISS-MODEL, MolProbity, ProSA, PyMol, and FATCAT tools. The most important mutation which was diagnosed in the woman (R1362Q mutation in the 35th exon of CACNA1F), was observed in her mother and her two uncles. The mutation was also screened in both her father and her fiancé, but they had no mutations. After medical examinations of carriers, there was no sign of any eye impairment. Other mutations were TCTN2 (c.1613-2A > G), TARS (p.K319E), SPEG (p.E3020K), CPS1 (p.A1180V), MYO3A (p.I736M), NNT (p.R968Q), MED23 (p.K406T). Bioinformatics analyses indicated no alteration in the mutant structure of CACNA1F (Q1362) compared with the normal structure (R1362). Conclusively, the current study emphasizes the non-pathogenic effect of missense mutation R1362Q in the 35th exon of CACNA1F in association with ocular diseases. This will ensure the reports of this mutation as healthy instead of uncertain in the literature and databanks.