# Decoding _Scn2a_ Variants: Bridging Genetics and Phenotypes in Autism Spectrum Disorder
## 6 Conclusions and Future Directions  
This systematic review highlights the critical role of _SCN2A_ mutations in ASD, shedding light on the intricate genotypic and phenotypic relationships that define its clinical manifestations. By analyzing data from 695 patients across 11 studies, the findings highlight the prevalence of _SCN2A_ mutations in ASD and their significant contribution to diverse neurological symptoms, including seizures, intellectual disability, motor impairments, and behavioral deficits. The identification of specific mutation types, such as missense mutations, frameshifts, and splicing abnormalities, and their association with distinct phenotypes provides valuable insights into the molecular underpinnings of ASD. Furthermore, the exploration of gender differences and mosaicism reveals additional layers of complexity in the clinical presentation, underscoring the need for personalized approaches in diagnosis and treatment.  
The findings presented here hold substantial clinical significance. By detailing genotype-phenotype correlations, this work provides a foundation for more precise genetic counseling and risk assessment for families affected by _SCN2A_-related disorders. Additionally, the identification of specific mutations, including novel variants, points to opportunities for the development of targeted therapies, particularly for severe manifestations such as early-onset epilepsy and profound intellectual disability. These insights could pave the way for precision medicine approaches that align therapeutic interventions with individual genetic profiles, improving outcomes for affected individuals.  
Future research directions include prospective, large-scale studies to validate genotype-phenotype correlations and further explore the impact of gender differences and mosaicism in _SCN2A_-related ASD. Functional studies investigating the biological effects of specific _SCN2A_ mutations will be crucial in identifying druggable targets and understanding the molecular mechanisms driving phenotypic variability. Additionally, integrating emerging technologies such as CRISPR-based gene editing and patient-derived neuronal models will allow for preclinical testing of novel therapeutic strategies tailored to _SCN2A_-related disorders [11].  
Expanding the diversity of study populations will also be essential to ensure the generalizability of findings across ethnic and demographic groups. The interdisciplinary collaboration among geneticists, neurologists, and behavioral scientists will be pivotal in translating these discoveries into clinical practice, ultimately improving the quality of life for individuals with _SCN2A_-related ASD and their families.  
Conceptualization, N.D., J.N.C., D.H.E., M.Z., J.M., D.C., A.M., R.H., A.S., R.M. and A.A.E.; methodology, N.D., J.N.C., D.H.E., M.Z., J.M., D.C., A.M., R.H., A.S., R.M. and A.A.E.; validation, N.D., J.N.C., D.H.E., M.Z., J.M., D.C., A.M., R.H., A.S., R.M. and A.A.E.; formal analysis, N.D., J.N.C., D.H.E., M.Z., J.M., D.C., A.M., R.H., A.S., R.M. and A.A.E.; investigation, N.D., J.N.C., D.H.E., M.Z., J.M., D.C., A.M., R.H., A.S., R.M. and A.A.E.; data curation, N.D., J.N.C., D.H.E., M.Z., J.M., D.C., A.M., R.H., A.S., R.M. and A.A.E.; writing--original draft preparation, N.D., J.N.C., D.H.E., M.Z., J.M., D.C., A.M., R.H., A.S., R.M. and A.A.E.; writing--review and editing, N.D., J.N.C., D.H.E., M.Z., J.M., D.C., A.M., R.H., A.S., R.M. and A.A.E.; supervision, R.M. and A.A.E.; project administration, R.M. and A.A.E. All authors have read and agreed to the published version of the manuscript.  
This research received no external funding.  
We are grateful to [PERSON] for the critical reading of the manuscript.  
The authors declare no conflicts of interest.