Unveiling a Novel THOC2 Mutation's Role in X-linked Intellectual Disability

Background: Intellectual disabilities encompass a spectrum of neurodevelopmental disorders profoundly impacting an individual's cognitive abilities, adaptive behaviors, and communication skills. This article delves into the complex challenges encountered by an individual with intellectual disability, particularly examining the interplay between cognitive limitations and speech difficulties, while presenting a case report detailing the experience of a son within a non-consanguineous family diagnosed with intellectual disability due to a new genetic defect in THOC2, thereby contributing significantly to our comprehension of THOC2-related pathogenic variants. Case presentation: A 14-year-old boy from a non-consanguineous Iranian family presented with significant challenges in academics, communication, and adaptive skills, accompanied by speech problems and exhibiting distinctive physical characteristics. The exome-sequencing analysis revealed a novel hemizygous c.1559+5A>T mutation located in intron 14 (NM_001081550.2) within the THOC2 gene in the proband. Sanger sequencing further confirmed the mother as a carrier of the mutation, although she remains in good health, while the father exhibits a normal genotype. This delineates an X-linked inheritance pattern, shedding light on the familial transmission of the identified genetic anomaly. Conclusion: The precise identification of the c.1559+5A>T splicing mutation in the THOC2 gene, achieved through exome-sequencing, conclusively diagnoses X-linked intellectual disability in our patient. This breakthrough not only unravels the molecular intricacies contributing to intellectual disability but also underscores the urgency for accurate and swift disease diagnosis.