{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:28:47Z","timestamp":1790555327967,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Francophonie University Agency (AUF)"},{"name":"National Council for Scientific Research in Lebanon (CNRSL)"},{"name":"Higher Center for Research of the Holy Spirit University of Kaslik (HCR-USEK)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Autism Spectrum Disorder (ASD) has become a major public health concern due to its rapidly rising incidence over the past few years. Disturbances in folate or methionine metabolism have been identified in many individuals with ASD, suggesting that the folate\u2013methionine cycle may play an essential role in the pathogenesis of autism. Thus, changes in metabolite concentrations associated with this cycle could be used as potential biomarkers and therapeutic targets for ASD. The aim of this systematic review is to elucidate the perturbations of this cycle and the possible interventions that may be proposed in this context. Several studies have shown that high levels of homocysteine and low levels of vitamins B12 and folate are associated with ASD. These changes in serum metabolites are influenced by poor diet. In fact, children with ASD tend to eat selectively, which could compromise the quality of their diet and result in nutrient deficiencies. Moreover, these disturbances may also be caused by genetic predispositions such as polymorphisms of the MTHFR gene. Few studies have demonstrated the beneficial effects of the use of nutritional supplements in treating ASD children. Therefore, larger, well-structured studies are recommended to examine the impact of vitamin B12 and folate supplementation on homocysteine levels.<\/jats:p>","DOI":"10.3390\/genes14030709","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T03:29:16Z","timestamp":1678764556000},"page":"709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Folate\u2013Methionine Cycle Disruptions in ASD Patients and Possible Interventions: A Systematic Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-2031","authenticated-orcid":false,"given":"Melissa","family":"Roufael","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, Holy Spirit University of Kaslik, Jounieh P.O. Box 446, Lebanon"},{"name":"UMR Inserm 1253 Ibrain, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Bitar","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, Holy Spirit University of Kaslik, Jounieh P.O. Box 446, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonna","family":"Sacre","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Sciences, Faculty of Arts and Sciences, Holy Spirit University of Kaslik, Jounieh P.O. Box 446, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5062-3156","authenticated-orcid":false,"given":"Christian","family":"Andres","sequence":"additional","affiliation":[{"name":"UMR Inserm 1253 Ibrain, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid","family":"Hleihel","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, Holy Spirit University of Kaslik, Jounieh P.O. Box 446, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/aur.2696","article-title":"Global prevalence of autism: A systematic review update","volume":"15","author":"Zeidan","year":"2022","journal-title":"Autism Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3389\/fnins.2018.00304","article-title":"Current Enlightenment About Etiology and Pharmacological Treatment of Autism Spectrum Disorder","volume":"12","author":"Eissa","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1007\/s10803-015-2590-7","article-title":"Prevalence of Autism Spectrum Disorder in Nurseries in Lebanon: A Cross Sectional Study","volume":"46","author":"Chaaya","year":"2016","journal-title":"J. Autism Dev. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.21037\/tp.2019.09.09","article-title":"Autism spectrum disorder: Definition, epidemiology, causes, and clinical evaluation","volume":"9","author":"Hodges","year":"2020","journal-title":"Transl. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"12096","DOI":"10.1038\/s41598-017-12317-3","article-title":"Chromosomal microarray analysis in a cohort of underrepresented population identifies SERINC2 as a novel candidate gene for autism spectrum disorder","volume":"7","author":"Hnoonual","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e786","DOI":"10.1002\/mgg3.786","article-title":"Identification of rare copy number variations reveals PJA2, APCS, SYNPO, and TAC1 as novel candidate genes in Autism Spectrum Disorders","volume":"7","author":"Bitar","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19088","DOI":"10.1038\/srep19088","article-title":"RYR2, PTDSS1 and AREG genes are implicated in a Lebanese population-based study of copy number variation in autism","volume":"6","author":"Soueid","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/S2215-0366(19)30181-6","article-title":"Environmental risk factors and biomarkers for autism spectrum disorder: An umbrella review of the evidence","volume":"6","author":"Kim","year":"2019","journal-title":"Lancet Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gerges, P., Bitar, T., Hawat, M., Alameddine, A., Soufia, M., Andres, C.R., and Hleihel, W. (2020). Risk and Protective Factors in Autism Spectrum Disorders: A Case Control Study in the Lebanese Population. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17176323"},{"key":"ref_10","unstructured":"Ming, X., Stein, T.P., Barnes, V., Rhodes, N., and Guo, L. (2022, June 20). Metabolic Perturbance in Autism Spectrum Disorders: A Metabolomics Study. Available online: https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/pr300910n."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jpba.2018.01.007","article-title":"Identification of metabolic pathway disturbances using multimodal metabolomics in autistic disorders in a Middle Eastern population","volume":"152","author":"Bitar","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ijdevneu.2015.06.006","article-title":"Abnormal transsulfuration metabolism and reduced antioxidant capacity in Chinese children with autism spectrum disorders","volume":"46","author":"Han","year":"2015","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1093\/ajcn\/80.6.1611","article-title":"Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism","volume":"80","author":"James","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jnutbio.2019.04.004","article-title":"The concomitant lower concentrations of vitamins B6, B9 and B12 may cause methylation deficiency in autistic children","volume":"70","author":"Belardo","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41398-019-0578-3","article-title":"Metabolomics analysis of children with autism, idiopathic-developmental delays, and Down syndrome","volume":"9","author":"Orozco","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lyon, P., Strippoli, V., Fang, B., and Cimmino, L. (2020). B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease. Nutrients, 12.","DOI":"10.3390\/nu12092867"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.3945\/ajcn.2009.29002","article-title":"Folate and methionine metabolism in autism: A systematic review","volume":"91","author":"Main","year":"2010","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12986-017-0233-z","article-title":"The metabolism and significance of homocysteine in nutrition and health","volume":"14","author":"Kumar","year":"2017","journal-title":"Nutr. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev-animal-020518-115206","article-title":"One-Carbon Metabolism: Linking Nutritional Biochemistry to Epigenetic Programming of Long-Term Development","volume":"7","author":"Clare","year":"2019","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1007\/s10803-021-04951-8","article-title":"Prenatal Folic Acid Supplements and Offspring\u2019s Autism Spectrum Disorder: A Meta-analysis and Meta-regression","volume":"52","author":"Liu","year":"2022","journal-title":"J. Autism Dev. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"W65","DOI":"10.7326\/0003-4819-151-4-200908180-00136","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration","volume":"151","author":"Liberati","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hoxha, B., Hoxha, M., Domi, E., Gervasoni, J., Persichilli, S., Malaj, V., and Zappacosta, B. (2021). Folic Acid and Autism: A Systematic Review of the Current State of Knowledge. Cells, 10.","DOI":"10.3390\/cells10081976"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e1960","DOI":"10.54905\/disssi\/v26i119\/ms40e1960","article-title":"Nutritional status among children with autism spectrum disorders in Saudi Arabia","volume":"26","author":"Alahmari","year":"2022","journal-title":"Med. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1177\/1362361318794179","article-title":"Differences in food consumption and nutritional intake between children with autism spectrum disorders and typically developing children: A meta-analysis","volume":"23","author":"Canals","year":"2019","journal-title":"Autism"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.rasd.2018.03.002","article-title":"Dietary status and nutrient intake of children with autism spectrum disorder: A case-control study","volume":"50","author":"Barnhill","year":"2018","journal-title":"Res. Autism Spectr. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Plaza-Diaz, J., Flores-Rojas, K., de la Torre-Aguilar, M.J., Gomez-Fern\u00e1ndez, A.R., Mart\u00edn-Borreguero, P., Perez-Navero, J.L., Gil, A., and Gil-Campos, M. (2021). Dietary Patterns, Eating Behavior, and Nutrient Intakes of Spanish Preschool Children with Autism Spectrum Disorders. Nutrients, 13.","DOI":"10.3390\/nu13103551"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s10803-017-3340-9","article-title":"Sensory sensitivity and food selectivity in children with autism spectrum disorder","volume":"48","author":"Chistol","year":"2018","journal-title":"J. Autism Dev. Disord."},{"key":"ref_28","first-page":"78","article-title":"Mealtime challenges and food selectivity in children with autism spectrum disorder in South Africa","volume":"35","author":"Adams","year":"2022","journal-title":"S. Afr. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1002\/eat.23631","article-title":"Food selectivity, nutritional inadequacies, and mealtime behavioral problems in children with autism spectrum disorder compared to neurotypical children","volume":"54","author":"Planells","year":"2021","journal-title":"Int. J. Eat Disord."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"598805","DOI":"10.3389\/fped.2021.598805","article-title":"Association between MTHFR C677T Polymorphism and Susceptibility to Autism Spectrum Disorders: A Meta-Analysis in Chinese Han Population","volume":"9","author":"Li","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5287","DOI":"10.19082\/5287","article-title":"Study of the C677T and 1298AC polymorphic genotypes of MTHFR Gene in autism spectrum disorder","volume":"9","author":"Kamal","year":"2017","journal-title":"Electron. Physician"},{"key":"ref_32","first-page":"247","article-title":"Study of MTHFR C677T Polymorphism and Associated Oxidative Stress Biomarkers among Autism Spectrum Disorder Patients in Jordan","volume":"13","author":"Hunaiti","year":"2020","journal-title":"Jordan J. Biol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Li, Y., Qiu, S., Shi, J., Guo, Y., Li, Z., Cheng, Y., and Liu, Y. (2020). Association between MTHFR C677T\/A1298C and susceptibility to autism spectrum disorders: A meta-analysis. BMC Pediatr., 20.","DOI":"10.1186\/s12887-020-02330-3"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ajp.2019.09.016","article-title":"Association of MTHFR 677C>T and 1298A>C polymorphisms with susceptibility to autism: A systematic review and meta-analysis","volume":"46","author":"Sadeghiyeh","year":"2019","journal-title":"Asian J. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101473","DOI":"10.1016\/j.rasd.2019.101473","article-title":"Association between MTHFR gene polymorphism and susceptibility to autism spectrum disorders: Systematic review and meta-analysis","volume":"70","author":"Razi","year":"2020","journal-title":"Res. Autism Spectr. Disord."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100585","DOI":"10.1016\/j.genrep.2019.100585","article-title":"Identification of MTHFR genetic polymorphism in Iraqi autistic children","volume":"18","author":"Muftin","year":"2020","journal-title":"Gene Rep."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Sun, C., Zou, M., Zhao, D., Xia, W., and Wu, L. (2016). Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial. Nutrients, 8.","DOI":"10.3390\/nu8060337"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"\u010corejov\u00e1, A., Fazeka\u0161, T., J\u00e1no\u0161\u00edkov\u00e1, D., Repisk\u00fd, J., Posp\u00ed\u0161ilov\u00e1, V., Mikov\u00e1, M., Rauov\u00e1, D., Ostatn\u00edkov\u00e1, D., Kyselovi\u010d, J., and Hrabovsk\u00e1, A. (2022). Improvement of the Clinical and Psychological Profile of Patients with Autism after Methylcobalamin Syrup Administration. Nutrients, 14.","DOI":"10.3390\/nu14102035"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1089\/cap.2015.0159","article-title":"Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism","volume":"26","author":"Hendren","year":"2016","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"383","DOI":"10.9758\/cpn.2018.16.4.383","article-title":"The Levels of Vitamin D, Vitamin D Receptor, Homocysteine and Complex B Vitamin in Children with Autism Spectrum Disorders","volume":"16","author":"Altun","year":"2018","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.2147\/NDT.S212361","article-title":"Comparison of serum B12, folate and homocysteine concentrations in children with autism spectrum disorder or attention deficit hyperactivity disorder and healthy controls","volume":"15","author":"Alpay","year":"2019","journal-title":"Neuropsychiatr. Dis. Treat"},{"key":"ref_42","first-page":"1718","article-title":"Food Selectivity in Autism Spectrum Disorders: A Systematic Review","volume":"29","author":"Zazpe","year":"2013","journal-title":"J. Child Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1515\/jomb-2017-0051","article-title":"Association between MTHFR 677C>T Polymorphism and Vitamin B12 Deficiency: A Case-control Study","volume":"37","author":"Zoubi","year":"2018","journal-title":"J. Med. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Raghubeer, S., and Matsha, T.E. (2021). Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks. Nutrients, 13.","DOI":"10.3390\/nu13124562"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s00702-021-02360-w","article-title":"Genetic risk factors for autism-spectrum disorders: A systematic review based on systematic reviews and meta-analysis","volume":"128","author":"Wei","year":"2021","journal-title":"J. Neural Transm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e5355","DOI":"10.1097\/MD.0000000000005355","article-title":"Combined genotype and haplotype distributions of MTHFR C677T and A1298C polymorphisms","volume":"95","author":"Fan","year":"2016","journal-title":"Medicine"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tisato, V., Silva, J.A., Longo, G., Gallo, I., Singh, A.V., Milani, D., and Gemmati, D. (2021). Genetics and epigenetics of one-carbon metabolism pathway in autism spectrum disorder: A sex-specific brain epigenome?. Genes, 12.","DOI":"10.3390\/genes12050782"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1007\/s00394-017-1528-6","article-title":"Supplement intervention associated with nutritional deficiencies in autism spectrum disorders: A systematic review","volume":"57","author":"Li","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_49","first-page":"31","article-title":"A Study of Plasma Homocysteine Level in Children with Autism","volume":"10","author":"Elaziz","year":"2022","journal-title":"Asian J. Pediatr. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e273","DOI":"10.1038\/tp.2013.51","article-title":"Redox metabolism abnormalities in autistic children associated with mitochondrial disease","volume":"3","author":"Frye","year":"2013","journal-title":"Transl. Psychiatry"},{"key":"ref_51","first-page":"243","article-title":"Role of Vitamin B12 in Autistic Spectrum and Attention Deficit Hyperactivity Disorders: A Scoping Review","volume":"8","author":"Rawat","year":"2021","journal-title":"Indian J. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3390\/nu2030299","article-title":"Vitamin B12 in Health and Disease","volume":"2","author":"Samman","year":"2010","journal-title":"Nutrients"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Robea, M.-A., Luca, A.-C., and Ciobica, A. (2020). Relationship between Vitamin Deficiencies and Co-Occurring Symptoms in Autism Spectrum Disorder. Medicina, 56.","DOI":"10.3390\/medicina56050245"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Parra, M., Stahl, S., and Hellmann, H. (2018). Vitamin B6 and Its Role in Cell Metabolism and Physiology. Cells, 7.","DOI":"10.3390\/cells7070084"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"687","DOI":"10.2217\/bmm-2017-0109","article-title":"Folate metabolism abnormalities in autism: Potential biomarkers","volume":"11","author":"Frye","year":"2017","journal-title":"Biomark. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/dneu.22579","article-title":"Folate Action in Nervous System Development and Disease","volume":"78","author":"Balashova","year":"2018","journal-title":"Dev. Neurobiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"101928","DOI":"10.1016\/j.rasd.2022.101928","article-title":"Interrelation of food selectivity, oral sensory sensitivity, and nutrient intake in children with autism spectrum disorder: A scoping review","volume":"93","author":"Zulkifli","year":"2022","journal-title":"Res. Autism Spectr. Disord."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1177\/1362361321995631","article-title":"Feeding and eating problems in children and adolescents with autism: A scoping review","volume":"25","author":"Baraskewich","year":"2021","journal-title":"Autism"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.rasd.2014.12.010","article-title":"Eating and feeding problems and gastrointestinal dysfunction in Autism Spectrum Disorders","volume":"12","author":"Vissoker","year":"2015","journal-title":"Res. Autism Spectr. Disord."},{"key":"ref_60","first-page":"e12586","article-title":"Clinical Relevance of Methylenetetrahydrofolate Reductase Genetic Testing in Autism: A Case Report of Successful Clinical Outcome","volume":"13","author":"Suman","year":"2021","journal-title":"Cureus"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1007\/s12098-022-04221-0","article-title":"A Treatable Cause of Global Developmental Delay with Autism Spectrum Disorder Due to Cobalamin Related Remethylation Disorder","volume":"89","author":"Gowda","year":"2022","journal-title":"Indian J. Pediatr."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/3\/709\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:54:08Z","timestamp":1760122448000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/3\/709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,13]]},"references-count":61,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["genes14030709"],"URL":"https:\/\/doi.org\/10.3390\/genes14030709","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,13]]}}}