WASF1, also known as WAVE1, is a key component of the WAVE regulatory complex (WRC) crucial for actin polymerization. It acts as a mediator between Rac-GTPase and actin, playing an essential role in regulating the dynamics of the actin cytoskeleton, which is involved in many cellular processes like cell motility [4,5].

Mutations in WASF1 have been linked to significant neurodevelopmental impacts. De novo truncating mutations in WASF1 were identified in individuals with moderate-to-profound intellectual disability, autistic features, and seizures. Functional studies using fibroblast cells from affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling, suggesting that WASF1 mutations cause a rare form of intellectual disability [4]. Additionally, several cases of neurodevelopmental disorder with absent language and variable seizures (NEDALVS) were associated with de novo mutations in WASF1. These include nonsense, missense, and copy-number variants in the gene [1,2,3,6].

In conclusion, WASF1 is vital for actin-related cellular functions. Research on WASF1, especially through functional studies in affected individuals, has revealed its significant role in neurodevelopmental disorders. Understanding WASF1's function and its mutations provides insights into the genetic basis of these disorders, potentially guiding future diagnostic and therapeutic strategies.

References:

1. Tang, Xiang, Liu, Guoqing, Lin, Li, Xiao, Nong, Chen, Yuxia. 2023. The recurrent WASF1 nonsense variant identified in two unaffected Chinese families with neurodevelopmental disorder: case report and review of the literatures. In BMC medical genomics, 16, 203. doi:10.1186/s12920-023-01630-8. https://pubmed.ncbi.nlm.nih.gov/37641121/

2. Zhao, Arman, Zhou, Rui, Gu, Qin, Wang, Hongying, Chen, Xuqin. 2021. Trio exome sequencing identified a novel de novo WASF1 missense variant leading to recurrent site substitution in a Chinese patient with developmental delay, microcephaly, and early-onset seizures: A mutational hotspot p.Trp161 and literature review. In Clinica chimica acta; international journal of clinical chemistry, 523, 10-18. doi:10.1016/j.cca.2021.08.030. https://pubmed.ncbi.nlm.nih.gov/34478686/

3. Srivastava, Siddharth, Macke, Erica L, Swanson, Lindsay C, Leppert, Mary L O, Cohen, Julie S. 2021. Expansion of the Genotypic and Phenotypic Spectrum of WASF1-Related Neurodevelopmental Disorder. In Brain sciences, 11, . doi:10.3390/brainsci11070931. https://pubmed.ncbi.nlm.nih.gov/34356165/

4. Ito, Yoko, Carss, Keren J, Duarte, Sofia T, Dyack, Sarah, Raymond, F Lucy. 2018. De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures. In American journal of human genetics, 103, 144-153. doi:10.1016/j.ajhg.2018.06.001. https://pubmed.ncbi.nlm.nih.gov/29961568/

5. Limaye, Ameya J, Whittaker, Matthew K, Bendzunas, George N, Cowell, John K, Kennedy, Eileen J. 2022. Targeting the WASF3 complex to suppress metastasis. In Pharmacological research, 182, 106302. doi:10.1016/j.phrs.2022.106302. https://pubmed.ncbi.nlm.nih.gov/35691539/

6. Shimojima Yamamoto, Keiko, Yanagishita, Tomoe, Yamamoto, Hisako, Sakata, Yasushi, Yamamoto, Toshiyuki. 2021. Recurrent de novo pathogenic variant of WASF1 in a Japanese patient with neurodevelopmental disorder with absent language and variable seizures. In Human genome variation, 8, 43. doi:10.1038/s41439-021-00176-4. https://pubmed.ncbi.nlm.nih.gov/34845217/