Narges Ghezelbash, Mortaza Bonyadi, Mohammad Hossein Jabbarpour Bonyadi
Retinitis pigmentosa (RP) is a genetically heterogeneous disease characterized by progressive vision loss and blindness, primarily due to the degeneration of cone photoreceptor cells. The classic symptoms include a decline in visual acuity and retinal atrophy. In this study, whole-exome sequencing (WES) was performed on a 40-year-old man from a nonconsanguineous Iranian-Azeri Turkish family, who was diagnosed with vision loss and blindness at age 40. DNA was extracted from the proband, his healthy brother, sister, and mother to conduct segregation analysis. WES analysis revealed a hemizygous mutation in a single nucleotide (NC_000023.11)(NM_001034853.2) c.194G>T, located in exon 3 of the RPGR gene. In silico analysis suggested that this mutation likely activates a new cryptic donor site. Segregation analysis confirmed that the variant was absent in the mother and healthy siblings, indicating that it is a de novo mutation. We also screened a cohort of 430 healthy individuals from the same ethnic group, finding no occurrence of the variant. The presence of this de novo mutation, its absence among controls from the same ethnic background, and bioinformatics analysis collectively suggest the pathogenicity of the identified variant.