ABSTRACT
BACKGROUND: X-linked mutations are highly important in clinical diagnosis, and at least 533 disorders are related to the genes located on the X chromosome. CASE PRESENTATION: A 21-year-old Caucasian woman with a 24-year-old Caucasian man as her fiancé referred Clinical genetic lab for premarital genetic counseling (carrier screening). None of them had any abnormal manifestations. Following genetic counseling, Whole Exome Sequencing (WES) test performed to find the possible pathogenic mutations. Also, after drawing the couple's pedigree, candidate mutations were examined in the woman's parents as well as her uncles. Additionally, in silico investigations were performed through SWISS-MODEL, MolProbity, ProSA, Py- Mol, and FATCAT tools. The most important mutation diagnosed in the woman (R1362Q 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). CONCLUSION: 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.
ABSTRACT
As the most common type of inherited retinal degenerative disease, retinitis pigmentosa (RP) has taken clinical and prenatal attention. Considering the clinical importance of consanguineous marriages, new mutations in this type of pregnancy have a high risk and increase the importance of Prenatal Diagnosis (PND). In vitro analysis was done through Whole Exome Sequencing (WES) for a 36-year-old woman who was referred to a genetic laboratory in Kermanshah in 2021 for PND. The woman had consanguineous marriage and was pregnant with twins (a boy and a girl). Mutation confirmation tests were also performed on her husband and both fetuses to find mutations. Moreover, in silico analyses were performed by SWISS-MODEL, ProSA, Molprobity, Swiss-Pdb Viewer, and ERRAT. The WES analysis showed a novel mutation of the RP2 gene (exon2:c. 359G>C: p.R120P) in the 36-year-old pregnant woman. Mutations identified in her husband and her twins revealed changes in protein conformations. Further modeling and validation evaluations showed the replacement of Arg by Pro at the 120th residue site of the cognate protein. For the first time, our report introduced a novel missense mutation in the RP2 gene associated with severe signs of RP in an Iranian family based on an X-linked recessive pattern of genetic inheritance. These findings may pave the way for a better diagnosis of RP in genetic counseling and PND.
