{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:47:03Z","timestamp":1760143623282,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Abdul Aziz City for Science and Technology (KACST), National Plan for Science and Technology and Innovation","award":["08-MED 510-02"],"award-info":[{"award-number":["08-MED 510-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impaired social skills and communication. Forkhead box protein P1 (FOXP1) is involved in the development of the brain and the pathogenesis of ASD. However, the function of FOXP1 within the brain remains unclear. The aim of this case\u2013control study was to evaluate whether FOXP1 could be used as a diagnostic biomarker for ASD. Method: Blood plasma was collected from children with ASD and age-matched controls. The enzyme-linked immunosorbent assay (ELISA) was used to determine the FOXP1 plasma levels in ASD and control groups. The behavioral and social impairments in children with ASD were assessed using the Childhood Autism Rating Scale (CARS) and the Social Responsiveness Scale (SRS). Spearman\u2019s correlation coefficient (r) was used to determine the correlation between different variables. Results: The plasma FOXP1 protein level was significantly decreased in children with ASD compared to the controls (p &lt; 0.001). CARS showed significant differences between the mild-to-moderate and severe subgroups, while the SRS showed no significant difference between the two subgroups. Moreover, both the mild-to-moderate and severe subgroups exhibited a substantial drop in plasma FOXP1 compared to the controls. ASD children older than six years old also showed a significantly decreased FOXP1 level, compared to those aged six years or less. Furthermore, no significant correlation between the FOXP1 level, CARS, and SRS was observed. However, a negative correlation was found between age and FOXP1 plasma level. Conclusions: We suggest that plasma FOXP1 may act as a potential biomarker for the prognosis of ASD severity and social communication impairment. Further research with a larger sample size is needed to clarify these associations and help diagnose or understand the underlying mechanism of ASD.<\/jats:p>","DOI":"10.3390\/jcm14207132","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:47:08Z","timestamp":1760104028000},"page":"7132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Examining the Potential Link Between Forkhead Box P1 and Severity and Social Impairment in Children with Autism Spectrum Disorder"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3269-0416","authenticated-orcid":false,"given":"Laila Yousef","family":"Al-Ayadhi","sequence":"first","affiliation":[{"name":"Autism Research and Treatment Center, Department of Physiology, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia"},{"name":"Department of Physiology, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8267-3804","authenticated-orcid":false,"given":"Nadra Elyass","family":"Elamin","sequence":"additional","affiliation":[{"name":"Autism Research and Treatment Center, Department of Physiology, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Durria Ahmed","family":"Abdulmaged","sequence":"additional","affiliation":[{"name":"Autism Research and Treatment Center, Department of Physiology, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurangzeb Taj","family":"Halepota","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7705-8348","authenticated-orcid":false,"given":"Dost Muhammad","family":"Halepoto","sequence":"additional","affiliation":[{"name":"Autism Research and Treatment Center, Department of Physiology, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (DMS-V), American Psychiatric Publishing Inc.. [5th ed.].","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wang, L., Wang, B., Wu, C., Wang, J., and Sun, M. (2023). Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031819"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e497","DOI":"10.1002\/mco2.497","article-title":"Autism spectrum disorder: Pathogenesis, biomarker, and intervention therapy","volume":"5","author":"Zhuang","year":"2024","journal-title":"MedComm"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/jdn.10356","article-title":"Neurocognitive features in childhood & adulthood in autism spectrum disorder: A Neurodiversity Approach","volume":"84","author":"Megari","year":"2024","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"El-Ansary, A., Alhakbany, M., Alfawaz, H.A., and Al-Ayadhi, L.Y. (2024). Indian Hedgehog (IHh) Protein and COX-2 as Biomarkers to Define the Mechanism of Epilepsy and Gastrointestinal Problems as Comorbid Medical Illnesses in Autism Spectrum Disorder: Combining ROC Curves to Improve Diagnostic Values. J. Clin. Med., 13.","DOI":"10.3390\/jcm13226695"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lv, T., Wang, M., Kui, L., Wu, J., and Xiao, Y. (2025). Novel Inflammatory Biomarkers for Autism Spectrum Disorder Detected by Plasma Olink Proteomics. Children, 12.","DOI":"10.3390\/children12020210"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Barbosa, A.G., Pratesi, R., Paz, G.S.C., dos Santos, M.A.A.L., Uenishi, R.H., Nakano, E.Y., Gandolfi, L., and Pratesi, C.B. (2020). Assessment of BDNF serum levels as a diagnostic marker in children with autism spectrum disorder. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-74239-x"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Noori, A.S., Rajabi, P., Sargolzaei, J., and Alaghmand, A. (2024). Correlation of biochemical markers and inflammatory cytokines in autism spectrum disorder (ASD). BMC Pediatr., 24.","DOI":"10.1186\/s12887-024-05182-3"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1007\/s12031-018-1192-1","article-title":"Diagnostic and Severity-Tracking Biomarkers for Autism Spectrum Disorder","volume":"66","author":"Meguid","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.cell.2019.12.036","article-title":"Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism","volume":"180","author":"Satterstrom","year":"2020","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eabd2827","DOI":"10.1126\/sciadv.abd2827","article-title":"Autism-linked gene FoxP1 selectively regulates the cultural transmission of learned vocalizations","volume":"7","author":"Koch","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/2040-2392-4-23","article-title":"Increased gene expression of FOXP1 in patients with autism spectrum disorders","volume":"4","author":"Chien","year":"2013","journal-title":"Mol. Autism"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13229-021-00469-z","article-title":"Individuals with FOXP1 syndrome present with a complex neurobehavioral profile with high rates of ADHD, anxiety, repetitive behaviors, and sensory symptoms","volume":"12","author":"Trelles","year":"2021","journal-title":"Mol. Autism"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1101\/gad.267989.115","article-title":"FoxP1 orchestration of ASD-relevant signaling pathways in the striatum","volume":"29","author":"Araujo","year":"2015","journal-title":"Genes Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s11689-021-09358-1","article-title":"FOXP1 syndrome: A review of the literature and practice parameters for medical assessment and monitoring","volume":"13","author":"Lozano","year":"2021","journal-title":"J. Neurodev. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1016\/j.celrep.2020.01.034","article-title":"Foxp1 Regulates Neural Stem Cell Self-Renewal and Bias Toward Deep Layer Cortical Fates","volume":"30","author":"Pearson","year":"2020","journal-title":"Cell Rep."},{"key":"ref_17","first-page":"e20595","article-title":"Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) With Language Impairment Accompanied by Developmental Disability Caused by Forkhead Box Protein 1 (FOXP1) Exon Deletion: A Case Report","volume":"13","author":"Alenezi","year":"2021","journal-title":"Cureus"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Benvenuto, M., Palumbo, P., Di Muro, E., Perrotta, C.S., Mazza, T., Mandar\u00e0, G.M.L., Palumbo, O., and Carella, M. (2023). Identification of a Novel FOXP1 Variant in a Patient with Hypotonia, Intellectual Disability, and Severe Speech Impairment. Genes, 14.","DOI":"10.3390\/genes14101958"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1136\/jmg-2023-109537","article-title":"Clinical phenotype of FOXP1 syndrome: Parent-reported medical signs and symptoms in 40 individuals","volume":"61","author":"Koene","year":"2024","journal-title":"J. Med. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104346","DOI":"10.1016\/j.braindev.2025.104346","article-title":"Autism-like features and FOXP1 syndrome: A scoping review","volume":"47","author":"Stewart","year":"2025","journal-title":"Brain Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13229-017-0172-6","article-title":"Prospective investigation of FOXP1 syndrome","volume":"8","author":"Siper","year":"2017","journal-title":"Mol. Autism"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1093\/hmg\/ddv495","article-title":"Identification and functional characterization of de novo FOXP1 variants provides novel insights into the etiology of neurodevelopmental disorder","volume":"25","author":"Sollis","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wang, J., Rappold, G.A., and Fr\u00f6hlich, H. (2022). Disrupted Mitochondrial Network Drives Deficits of Learning and Memory in a Mouse Model of FOXP1 Haploinsufficiency. Genes, 13.","DOI":"10.3390\/genes13010127"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ajhg.2010.09.017","article-title":"De Novo Mutations in FOXP1 in Cases with Intellectual Disability, Autism, and Language Impairment","volume":"87","author":"Hamdan","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Park, S.H.E., Kulkarni, A., and Konopka, G. (2023). FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells. PLoS Biol., 21.","DOI":"10.1371\/journal.pbio.3001852"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/s41588-022-01148-2","article-title":"Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes","volume":"54","author":"Zhou","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1523\/JNEUROSCI.0222-19.2019","article-title":"NEXMIF\/KIDLIA Knock-out Mouse Demonstrates Autism-Like Behaviors, Memory Deficits, and Impairments in Synapse Formation and Function","volume":"40","author":"Gilbert","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1038\/mp.2014.116","article-title":"Brain-specific Foxp1 deletion impairs neuronal development and causes autistic-like behavior","volume":"20","author":"Bacon","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10917","DOI":"10.1523\/JNEUROSCI.1005-17.2017","article-title":"Foxp1 in Forebrain Pyramidal Neurons Controls Gene Expression Required for Spatial Learning and Synaptic Plasticity","volume":"37","author":"Araujo","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"22237","DOI":"10.1073\/pnas.1911429116","article-title":"Gastrointestinal dysfunction in autism displayed by altered motility and achalasia in Foxp1+\/\u2212 mice","volume":"116","author":"Kollmeyer","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eaat7615","DOI":"10.1126\/science.aat7615","article-title":"Integrative functional genomic analysis of human brain development and neuropsychiatric risks","volume":"362","author":"Li","year":"2018","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e00789","DOI":"10.1002\/mgg3.789","article-title":"Pathogenic missense mutation pattern of forkhead box genes in neurodevelopmental disorders","volume":"7","author":"Han","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13229-023-00567-0","article-title":"Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism","volume":"14","author":"Li","year":"2023","journal-title":"Mol. Autism"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shiota, Y., Nishiyama, T., Yokoyama, S., Yoshimura, Y., Hasegawa, C., Tanaka, S., Iwasaki, S., and Kikuchi, M. (2024). Association of genetic variants with autism spectrum disorder in Japanese children revealed by targeted sequencing. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1352480"},{"key":"ref_35","unstructured":"Mick, K.A. (2005). Diagnosing Autism: Comparison of the Childhood Autism Rating Scale (CARS) and the Autism Diagnostic Observation Schedule (ADOS). [Ph.D. Dissertation, Wichita State University]."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1023\/A:1025014929212","article-title":"Validation of a Brief Quantitative Measure of Autistic Traits: Comparison of the Social Responsiveness Scale with the Autism Diagnostic Interview-Revised","volume":"33","author":"Constantino","year":"2003","journal-title":"J. Autism Dev. Disord."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e2112852119","DOI":"10.1073\/pnas.2112852119","article-title":"Mitochondrial dysfunction and oxidative stress contribute to cognitive and motor impairment in FOXP1 syndrome","volume":"119","author":"Wang","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bonsi, P., De Jaco, A., Fasano, L., and Gubellini, P. (2022). Postsynaptic autism spectrum disorder genes and synaptic dysfunction. Neurobiol. Dis., 162.","DOI":"10.1016\/j.nbd.2021.105564"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"114329","DOI":"10.1016\/j.celrep.2024.114329","article-title":"Five autism-associated transcriptional regulators target shared loci proximal to brain-expressed genes","volume":"43","author":"Darbandi","year":"2024","journal-title":"Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"115384","DOI":"10.1016\/j.celrep.2025.115384","article-title":"Cell-type-specific roles of FOXP1 in the excitatory neuronal lineage during early neocortical murine development","volume":"44","author":"Ortiz","year":"2025","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Co, M., Anderson, A.G., and Konopka, G. (2020). FOXP transcription factors in vertebrate brain development, function, and disorders. Wiley Interdiscip. Rev. Dev. Biol., 9.","DOI":"10.1002\/wdev.375"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/20\/7132\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:03:46Z","timestamp":1760105026000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/20\/7132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":41,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["jcm14207132"],"URL":"https:\/\/doi.org\/10.3390\/jcm14207132","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,10]]}}}