Unraveling the role of NOG gene in hereditary sensory neuropathy type 1F through CRISPR/Cas9-mediated ATL3 knockout

Abstract Background ATL3 pathogenic variations cause hereditary sensory neuropathy type 1F (HSN1F), an autosomal dominant disorder characterized by distal sensory dysfunction manifesting as numbness, tingling, or discomfort. The ATL3 gene encodes the Atl3 protein, which is a member of the ATL family of GTPases and plays a critical role in maintaining the stability and homeostasis of sensory neurons. Up to now, eight unrelated families with ATL3 pathogenic variants causing HSN1F have been reported in the literature. Studies reported that the patients had missense, nonsense, and deletion mutations. To unravel the role of Noggin (NOG) gene in hereditary sensory neuropathy type 1F, this study was conducted through knocking out ATL3 in HeLa cells. This study was conducted after the clinical and molecular investigations of six patients from two unrelated Iranian families with a novel HSNIF nonsense variant. We have employed an ATL3 knockout approach to investigate the role of NOG in HSN1F pathology by using Clustered regularly interspaced palindromic repeats (CRISPR/Cas9) gene editing technology. Results A novel CRISPR-based cell model for HSN1F was designed to provide an appropriate foundation for further studies on the molecular mechanisms of Atl3 functions and a better comprehension of the disease pathogenesis. Conclusion Our study shows that the identified mutation has a detrimental effect on the normal expression of ATL3 . Furthermore, this investigation revealed that the ATL3 mutation caused an increase in the expression of the NOG .