IDENTIFICATION AND BIOINFORMATICS ANALYSIS OF TWO NOVEL VARIANTS IN THE SEMA4A AND SCP2 GENES IN A PATIENT WITH EARLY-ONSET VISUAL IMPAIRMENT AND LEUKODYSTROPHY.

Abstract

Optic Nerve Atrophy (ONA) is the destruction of the nerve fibers of the optic nerve, reducing the number of retinal ganglion cells that generate nerve impulses and transmit them from the eye to the brain. In this case, the information arriving in the brain is distorted, which is accompanied by deterioration of vision and can lead to irreversible blindness.

We conducted a genetic analysis of a six-year-old male patient with vision problems, cognitive impairment and leukodystrophy. DNA samples were collected from the patient and his mother and father. Whole-genome sequencing (WES) and PCR-Sanger sequencing were used to identify genetic variants. Two novel mutation variants were detected in the patient: a frameshift mutation in the SEMA4A gene (NM_001193300.2):c.2272_2273insT and a substitution in the SCP2 gene (NM_002979.5):c.712A>T. These mutations were confirmed in the parents and were not detected in the control group, which consists of 400 healthy people from the same ethnic group. In addition, such variants were absent from other published genetic databases, including 1000 Genomes, ExAc, gnomAD, and Iranome. Extensive bioinformatics analysis, the absence of these mutations in healthy human controls, and the early onset of symptoms confirm the pathogenicity of these variants.