Document Type : Review Article

Author

Clinical Medicine, Qingdao Medical College, Qingdao University, Qingdao, China

10.55705/cmbr.2025.449757.1243

Abstract

Autism, as a neurodevelopmental disorder, has become an important public health issue worldwide. The mechanisms by which DNA methylation regulates gene expression contributing to autism are complex and elaborate. As a non-invasive, highly accurate prenatal diagnosis, DNA methylation screening can be used to detect whether the fetus may be at risk for autism. However, the results of this approach require a professional bioinformatics analysis, and the diagnosis cannot be directly confirmed. Therefore, DNA methylation screening is often used as an adjunct to prenatal diagnosis rather than the only diagnostic basis. In practice, doctors will make a comprehensive judgment based on the results of DNA methylation screening, combined with other prenatal diagnosis methods, such as gene sequencing. Some studies have found a large number of DNA methylation abnormalities in the autistic brain, especially in genes related to neurodevelopment. These aberrant DNA methylation states may contribute to autism by affecting the expression of these genes, which in turn affects neuronal function and behavior. This study aimed to investigate the role of DNA methylation in autism and the application of detection techniques.

Graphical Abstract

Advanced Research on DNA methylation testing in screening fetuses for autism spectrum disorder

Keywords

Main Subjects

Selected author of this article by journal

Dr. Yulu Han
Qingdao University

ORCID

Open Access

This article is licensed under a CC BY License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit: http://creativecommons.org/licenses/by/4.0/

 

Publisher’s Note

CMBR journal remains neutral with regard to jurisdictional claims in published maps and institutional afflictions.

 

Letters to Editor

Given that CMBR Journal's policy in accepting articles will be strict and will do its best to ensure that in addition to having the highest quality published articles, the published articles should have the least similarity (maximum 15%). Also, all the figures and tables in the article must be original and the copyright permission of images must be prepared by authors. However, some articles may have flaws and have passed the journal filter, which dear authors may find fault with. Therefore, the editor of the journal asks the authors, if they see an error in the published articles of the journal, to email the article information along with the documents to the journal office.

CMBR Journal welcomes letters to the editor ([email protected], [email protected]) for the post-publication discussions and corrections which allows debate post publication on its site, through the Letters to Editor. Critical letters can be sent to the journal editor as soon as the article is online. Following points are to be considering before sending the letters (comments) to the editor.

[1] Letters that include statements of statistics, facts, research, or theories should include appropriate references, although more than three are discouraged.

[2] Letters that are personal attacks on an author rather than thoughtful criticism of the author’s ideas will not be considered for publication.

[3] There is no limit to the number of words in a letter.

[4] Letter writers should include a statement at the beginning of the letter stating that it is being submitted either for publication or not.

[5] Anonymous letters will not be considered.

[6] Letter writers must include Name, Email Address, Affiliation, mobile phone number, and Comments.

[7] Letters will be answered as soon as possible.

  1. Luo H, Wei W, Ye Z, Zheng J, Xu RH (2021) Liquid Biopsy of Methylation Biomarkers in Cell-Free DNA. Trends Mol Med 27 (5): 482-500. doi: https://doi.org/10.1016/j.molmed.2020.12.011
  2. Wang A, Ma Q, Gong B, Sun L, Afrim FK, Sun R, He T, Huang H, Zhu J, Zhou G, Ba Y (2021) DNA methylation and fluoride exposure in school-age children: Epigenome-wide screening and population-based validation. Ecotoxicol Environ Saf 223: 112612. doi: https://doi.org/10.1016/j.ecoenv.2021.112612
  3. Lord C, Brugha TS, Charman T, Cusack J, Dumas G, Frazier T, Jones EJH, Jones RM, Pickles A, State MW, Taylor JL, Veenstra-VanderWeele J (2020) Autism spectrum disorder. Nature Reviews Disease Primers 6 (1): 5. doi: https://doi.org/10.1038/s41572-019-0138-4
  4. Xu Y, Huang Z, Yu X, Chen K, Fan Y (2021) Integrated genomic and DNA methylation analysis of patients with advanced non-small cell lung cancer with brain metastases. Molecular Brain 14 (1): 176. doi: https://doi.org/10.1186/s13041-021-00886-4
  5. Xu Y, Zhao W, Mo Y, Ma N, Midorikawa K, Kobayashi H, Hiraku Y, Oikawa S, Zhang Z, Huang G, Takeuchi K, Murata M (2020) Combination of RERG and ZNF671 methylation rates in circulating cell-free DNA: A novel biomarker for screening of nasopharyngeal carcinoma. Cancer Sci 111 (7): 2536-2545. doi: https://doi.org/10.1111/cas.14431
  6. Zhang G, He F, Zhao G, Huang Z, Li X, Xia X, Guo Y, Xu W, Xiong S, Ma Y, Zheng M, Liu W (2021) Combining Serum DNA Methylation Biomarkers and Protein Tumor Markers Improved Clinical Sensitivity for Early Detection of Colorectal Cancer. Int J Genomics 2021: 6613987. doi: https://doi.org/10.1155/2021/6613987
  7. McKenney EE, Brunwasser SM, Richards JK, Day TC, Kofner B, McDonald RG, Williams ZJ, Gillespie-Lynch K, Kang E, Lerner MD, Gotham KO (2023) Repetitive Negative Thinking As a Transdiagnostic Prospective Predictor of Depression and Anxiety Symptoms in Neurodiverse First-Semester College Students. Autism in adulthood : challenges and management 5 (4): 374-388. doi: https://doi.org/10.1089/aut.2022.0078
  8. Rasmussen EMK, Seier KL, Pedersen IK, Kreibich C, Amdam GV, Münch D, Dahl JA (2021) Screening bioactive food compounds in honey bees suggests curcumin blocks alcohol-induced damage to longevity and DNA methylation. Scientific Reports 11 (1): 19156. doi: https://doi.org/10.1038/s41598-021-98614-4
  9. Lago C, Ballabio C, Miele E, Tiberi L (2022) MODL-13. Patient-derived organoids for modeling pediatric brain tumors. Neuro-Oncology 24 (Supplement_1): i171-i171. doi: https://doi.org/10.1093/neuonc/noac079.636
  10. Zhang D, He N, Yang X, Zhang D, Li Q, Xiong Y (2022) Research advance on the important role of selenoproteinin human health. Chinese Science Bulletin 67 (6): 473-480. doi: https://doi.org/10.1360/TB-2021-1019
  11. Wang X, Dong Y, Zhang H, Zhao Y, Miao T, Mohseni G, Du L, Wang C (2024) DNA methylation drives a new path in gastric cancer early detection: Current impact and prospects. Genes Dis 11 (2): 847-860. doi: https://doi.org/10.1016/j.gendis.2023.02.038
  12. Li Q, Jiang W, Zhang Y, Yang X, Huang T, Huang Y, Yang S, Wang Q (2023) Methylation of Septin9, SRSF1, and PAX8 in Early Screening of Colorectal Cancer in the Population Undergoing Physical Examinations. Clinical laboratory 69 (12). doi: https://doi.org/10.7754/Clin.Lab.2023.230426
  13. Mohapatra SS, Fioravanti A, Vandame P, Spriet C, Pini F, Bompard C, Blossey R, Valette O, Biondi EG (2020) Methylation-dependent transcriptional regulation of crescentin gene (creS) by GcrA in Caulobacter crescentus. Mol Microbiol 114 (1): 127-139. doi: https://doi.org/10.1111/mmi.14500
  14. Schotten LM, Darwiche K, Seweryn M, Yildiz V, Kneuertz PJ, Eberhardt WEE, Eisenmann S, Welter S, Sisson BE, Pietrzak M, Wiesweg M, Ploenes T, Hager T, He K, Freitag L, Aigner C, Taube C, Oezkan F (2021) DNA methylation of PTGER4 in peripheral blood plasma helps to distinguish between lung cancer, benign pulmonary nodules and chronic obstructive pulmonary disease patients. European journal of cancer (Oxford, England : 1990) 147: 142-150. doi: https://doi.org/10.1016/j.ejca.2021.01.032
  15. Li B, Guo R, Lai T, Qiao L, Fu H (2021) The application of PAX1 methylation detection and HPV E6/E7 mRNA detection in cervical cancer screening. The journal of obstetrics and gynaecology research 47 (8): 2720-2728. doi: https://doi.org/10.1111/jog.14869
  16. Sunny SK, Zhang H, Mzayek F, Arshad SH, Holloway J (2020) DNA Methylation at Earlier Ages Is Associated with Lung Function Later in Life. doi:https://doi.org/10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A4605
  17. Xie H, Yin W, Zheng Y, Zhang Y, Qin H, Huang Z, Zhao M, Li J (2024) Increased DNA methylation of the splicing regulator SR45 suppresses seed abortion in litchi. J Exp Bot 75 (3): 868-882. doi: https://doi.org/10.1093/jxb/erad427
  18. Pekkarinen M, Nordfors K, Uusi-Makela J, Kytola V, Hartewig A, Huhtala L, Rauhala M, Urhonen H, Hayrynen S, Afyounian E, Yli-Harja O, Zhang W, Helen P, Lohi O, Haapasalo H, Haapasalo J, Nykter M, Kesseli J, Rautajoki KJ (2024) Aberrant DNA methylation distorts developmental trajectories in atypical teratoid/rhabdoid tumors. Life science alliance 7 (6). doi: https://doi.org/10.26508/lsa.202302088
  19. Filho M, Reis M, Beltrami C, Mello J, Marchi F, Kuasne H, Drigo S, Andrade V, Saieg M, Pinto C, Kowalski L, Rogatto S (2019) DNA Methylation-Based Method to Differentiate Malignant from Benign Thyroid Lesions. Thyroid 29. doi: https://doi.org/10.1089/thy.2018.0458
  20. Hansen C, Drong A, Starnawska A, Grauholm J, Buil A, Weinsheimer S, Bækvad-Hansen M, Hougaard D, Lindgren C, Werge T (2019) Estimated DNA methylation gestational age in newborn monozygotic twins associate with later psychiatric disorders between con/discordant pairs. European Neuropsychopharmacology 29: S795. doi: https://doi.org/10.1016/j.euroneuro.2017.08.027
  21. Tang L, Liou Y-L, Wan Z-R, Tang J, Zhou Y, Zhuang W, Wang G (2019) Aberrant DNA methylation of PAX1, SOX1 and ZNF582 genes as potential biomarkers for esophageal squamous cell carcinoma. Biomedicine & Pharmacotherapy 120: 109488. doi: https://doi.org/10.1016/j.biopha.2019.109488
  22. Nordin A, Pagella P, Zambanini G, Cantu C (2024) Exhaustive identification of genome-wide binding events of transcriptional regulators. Nucleic Acids Res 52 (7): e40. doi: https://doi.org/10.1093/nar/gkae180
  23. Hnoonual A, Plong-On O, Worachotekamjorn J, Charalsawadi C, Limprasert P (2024) Clinical and molecular characteristics of FMR1 microdeletion in patient with fragile X syndrome and review of the literature. Clinica chimica acta; international journal of clinical chemistry 553: 117728. doi: https://doi.org/10.1016/j.cca.2023.117728
  24. Muhammad JS, Khan MR, Ghias K (2018) DNA methylation as an epigenetic regulator of gallbladder cancer: An overview. International journal of surgery (London, England) 53: 178-183. doi: https://doi.org/10.1016/j.ijsu.2018.03.053
  25. Ibrahim J, Peeters M, Van Camp G, Op de Beeck K (2023) Methylation biomarkers for early cancer detection and diagnosis: Current and future perspectives. European Journal of Cancer 178: 91-113. doi: https://doi.org/10.1016/j.ejca.2022.10.015
  26. Ohi K, Shimada M, Soda M, Nishizawa D, Fujikane D, Takai K, Kuramitsu A, Muto Y, Sugiyama S, Hasegawa J, Kitaichi K, Ikeda K, Shioiri T (2024) Genome-wide DNA methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorder. BMJ mental health 27 (1). doi: https://doi.org/10.1136/bmjment-2023-300936
  27. Syed S, Gragnoli C (2024) The glucocorticoid receptor gene (NR3C1) is linked to and associated with polycystic ovarian syndrome in Italian families. Journal of ovarian research 17 (1): 13. doi: https://doi.org/10.1186/s13048-023-01329-5
  28. Skiba SA, Hansen A, McCall R, Byers A, Waldron S, Epping AJ, Taglialatela JP, Hudson ML (2023) Linked OXTR Variants Are Associated with Social Behavior Differences in Bonobos (Pan paniscus). bioRxiv 2023: 56-98. doi: https://doi.org/10.1101/2023.12.22.573122
  29. Helderman NC, Andini KD, van Leerdam ME, van Hest LP, Hoekman DR, Ahadova A, Bajwa-Ten Broeke SW, Bosse T, van der Logt EMJ, Imhann F, Kloor M, Langers AMJ, Smit V, Terlouw D, van Wezel T, Morreau H, Nielsen M (2024) MLH1 Promotor Hypermethylation in Colorectal and Endometrial Carcinomas from Patients with Lynch Syndrome. The Journal of molecular diagnostics : JMD 26 (2): 106-114. doi: https://doi.org/10.1016/j.jmoldx.2023.10.005
  30. Heeke S, Gay CM, Estecio MR, Tran H, Morris BB, Zhang B, Tang X, Raso MG, Rocha P, Lai S, Arriola E, Hofman P, Hofman V, Kopparapu P, Lovly CM, Concannon K, De Sousa LG, Lewis WE, Kondo K, Hu X, Tanimoto A, Vokes NI, Nilsson MB, Stewart A, Jansen M, Horváth I, Gaga M, Panagoulias V, Raviv Y, Frumkin D, Wasserstrom A, Shuali A, Schnabel CA, Xi Y, Diao L, Wang Q, Zhang J, Van Loo P, Wang J, Wistuba, II, Byers LA, Heymach JV (2024) Tumor- and circulating-free DNA methylation identifies clinically relevant small cell lung cancer subtypes. Cancer Cell. doi: https://doi.org/10.1016/j.ccell.2024.01.001
  31. Zheng Y, Ziman B, Ho AS, Sinha UK, Xu LY, Li EM, Koeffler HP, Berman BP, Lin DC (2023) Comprehensive analyses of partially methylated domains and differentially methylated regions in esophageal cancer reveal both cell-type- and cancer-specific epigenetic regulation. Genome Biol 24 (1): 193. doi: https://doi.org/10.1186/s13059-023-03035-3
  32. Xu Y, Li X, Yang Y, Li C, Shao X (2019) Human age prediction based on DNA methylation of non-blood tissues. Computer methods and programs in biomedicine 171: 11-18. doi: https://doi.org/10.1016/j.cmpb.2019.02.010
  33. Buitrago D, Labrador M, Arcon JP, Lema R, Flores O, Esteve-Codina A, Blanc J, Villegas N, Bellido D, Gut M, Dans PD, Heath SC, Gut IG, Brun Heath I, Orozco M (2021) Impact of DNA methylation on 3D genome structure. Nature Communications 12 (1): 3243. doi: https://doi.org/10.1038/s41467-021-23142-8
  34. Qiu WR, Qi BB, Lin WZ, Zhang SH, Yu WK, Huang SF (2022) Predicting the Lung Adenocarcinoma and Its Biomarkers by Integrating Gene Expression and DNA Methylation Data. Front Genet 13: 926927. doi: https://doi.org/10.3389/fgene.2022.926927
  35. Pan Y, Lin H, Jiao H, Zhao J, Wang X (2023) Effects of in ovo feeding of chlorogenic acid on antioxidant capacity of postnatal broilers. Front Physiol 14: 1091520. doi: https://doi.org/10.3389/fphys.2023.1091520
  36. Sun M, Yang Z, Liu L, Duan L (2022) DNA Methylation in Plant Responses and Adaption to Abiotic Stresses. Int J Mol Sci 23 (13): 32-45. doi: https://doi.org/10.3390/ijms23136910
  37. Du C, Tan L, Xiao X, Xin B, Xiong H, Zhang Y, Ke Z, Yin J (2024) Detection of the DNA methylation of seven genes contribute to the early diagnosis of lung cancer. Journal of Cancer Research and Clinical Oncology 150 (2): 77. doi: https://doi.org/10.1007/s00432-023-05588-z
  38. He W, Zhang Y, Wu K, Wang Y, Zhao X, Lv L, Ren C, Lu J, Yang J, Yin A, Liu G (2023) Epigenetic phenotype of plasma cell-free DNA in the prediction of early-onset preeclampsia. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 43 (2): 2282100. doi: https://doi.org/10.1080/01443615.2023.2282100
  39. Zhou T, Wang X, Kong J, Yu L, Xie H, Wang F, Xu S, Shuai Z, Zhou Q, Pan F (2023) PRICKLE1 gene methylation and abnormal transcription in Chinese patients with ankylosing spondylitis. Immunobiology 228: 152742. doi: https://doi.org/10.1016/j.imbio.2023.152742
  40. Shen H, Liu Y, Wang C, Wang R, Di Z, Huang X, Zhang H, Liu M (2023) Prenatal diagnosis of 46,XX testicular disorder of sex development with SRY-positive: A case report and review of the literature. Eur J Obstet Gynecol Reprod Biol 289: 140-144. doi: https://doi.org/10.1016/j.ejogrb.2023.08.393
  41. Feng C, Liang W, Liu F, Xiong Y, Chen M, Feng P, Guo M, Wang Y, Li Z, Zhang L (2022) A Simple and Highly Sensitive Naked-Eye Analysis of EGFR 19del via CRISPR/Cas12a Triggered No-Nonspecific Nucleic Acid Amplification. ACS Synth Biol 11 (2): 867-876. doi: https://doi.org/10.1021/acssynbio.1c00521
  42. He Z, Tong Z, Tan B, He X, Zhang T, Guo Y, Jin L, He N, Li S, Chen Z (2021) Rapid Detection of DNA Methylation with a Novel Real-Time Fluorescence Recombinase-Aided Amplification Assay. J Biomed Nanotechnol 17 (7): 1364-1370. doi: https://doi.org/10.1166/jbn.2021.3111
  43. Smith J, Day RC, Weeks RJ (2022) Next-Generation Bisulfite Sequencing for Targeted DNA Methylation Analysis. Methods in molecular biology (Clifton, NJ) 2458: 47-62. doi: https://doi.org/10.1007/978-1-0716-2140-0_3
  44. Li J, Yang T, Hong C, Yang Z, Wu L, Gao Q, Yang H, Tan W (2022) Whole-Genome Sequencing for Resistance Level Prediction in Multidrug-Resistant Tuberculosis. Microbiol Spectr 10 (3): e0271421. doi: https://doi.org/10.1128/spectrum.02714-21
  45. Gorska A, Urbanowicz M, Grochowalski L, Seweryn M, Sobalska-Kwapis M, Wojdacz T, Lange M, Gruchala-Niedoszytko M, Jarczak J, Strapagiel D, Gorska-Ponikowska M, Pelikant-Malecka I, Kalinowski L, Nedoszytko B, Gutowska-Owsiak D, Niedoszytko M (2023) Genome-Wide DNA Methylation and Gene Expression in Patients with Indolent Systemic Mastocytosis. Int J Mol Sci 24 (18). doi: https://doi.org/10.3390/ijms241813910
  46. Feinberg JI, Schrott R, Ladd-Acosta C, Newschaffer CJ, Hertz-Picciotto I, Croen LA, Daniele Fallin M, Feinberg AP, Volk HE (2024) Epigenetic changes in sperm are associated with paternal and child quantitative autistic traits in an autism-enriched cohort. Mol Psychiatry 29 (1): 43-53. doi: https://doi.org/10.1038/s41380-023-02046-7
  47. Polakkattil BK, Vellichirammal NN, Nair IV, Nair CM, Banerjee M (2024) Methylome-wide and meQTL analysis helps to distinguish treatment response from non-response and pathogenesis markers in schizophrenia. Front Psychiatry 15: 1297760. doi: https://doi.org/10.3389/fpsyt.2024.1297760
  48. Tang J, Han J, Xue J, Zhen L, Yang X, Pan M, Hu L, Li R, Jiang Y, Zhang Y, Jing X, Li F, Chen G, Zhang K, Zhu F, Liao C, Lu L (2023) A Deep-Learning-Based Method Can Detect Both Common and Rare Genetic Disorders in Fetal Ultrasound. Biomedicines 11 (6). doi: https://doi.org/10.3390/biomedicines11061756
  49. Rather RA, Saha SC (2023) Reappraisal of evolving methods in non-invasive prenatal screening: Discovery, biology and clinical utility. Heliyon 9 (3): e13923. doi: https://doi.org/10.1016/j.heliyon.2023.e13923
  50. Paul LT, Ergoren MC (2022) Comparison of Bioinformatics Approaches for Fetal Microdeletions and Monogenic Variations Estimation in Non-invasive Prenatal Testing. Global medical genetics 9 (2): 72-75. doi: https://doi.org/10.1055/s-0042-1743573
  51. Al-Beltagi M (2023) Pre-autism: What a paediatrician should know about early diagnosis of autism. World journal of clinical pediatrics 12 (5): 273-294. doi: https://doi.org/10.5409/wjcp.v12.i5.273