{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:04:44Z","timestamp":1753862684903,"version":"3.41.2"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neural tube defects (NTDs) are defined as an incomplete closure of the neural tube (NT), with a prevalence of 1.2 per 1000 live births around the world. Methylation of the maternally imprinted gene Insulin\u2010like growth factor 2 (IGF2) is one of the epigenetic mechanisms that contribute significantly to the development of NTDs. Its important functions are the fetal growth and metabolism, as well as cell division and differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>In a couple of studies, individual changes in IGF2 with single nucleotide variants (SNVs) have been found to be linked with NTDs as well as with other diseases. However, there is more need of studying so that we can better understand precisely this mechanism at the molecular level. In this study we tried to investigate the relationship between genetic variants of IGF2 and NT closure by screening all SNVs of IGF2 using both in silico methods and clinical experiments on human samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled 98 consecutive mothers carrying fetuses with NTDs as cases and 76 age\u2010matched mothers with healthy babies as controls. Following an in silico analysis of the IGF2 gene, we designed three primers targeting a total of 180 exonic, 579 intronic, and 46 variants in the 3\u2032 untranslated region (3\u2032 UTR) for polymerase chain reaction (PCR) and subsequent sequencing. Statistical analyses were performed to assess associations between these genetic variants and NTDs. Additionally, quantitative real\u2010time PCR (qRT\u2010PCR) was conducted to analyze the mRNA expression levels of the target gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This is the first study to enlist 11 non\u2010synonymous variants [rs750845881(D93N), rs1290256492(P87H), rs755066389(P87T), rs150610908(G65D), rs762200142(R64C), rs868067982(G49C), rs778465733(R48L), rs1018841144(R48C), rs1057518115(C33R), rs112276039(C22R), rs1240151267(L16W)] in the regulation of IGF2 gene functions through in silico analysis. Further clinical validation in maternal samples showed a significant association between rs3213225 (C\u2009&gt;\u2009T) (OR\u20102.076; CI\u20101.123\u20103.840; <jats:italic>p<\/jats:italic>\u20100.0209) and rs734351 (C\u2009&gt;\u2009T) (OR\u20102.148; CI\u20101.167\u20103.956; <jats:italic>p<\/jats:italic>\u20100.0148) with increased disease risk. RNA expression study validated and supported all of these SNVs, indicating a strong correlation with NTD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our research strongly suggests that genetic variations in IGF2 may help explain the risk association with NTDs and could be valuable for diagnostic and therapeutic applications.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2428","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T06:01:27Z","timestamp":1736229687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Variants of <scp>IGF2<\/scp> Gene Are Linked With Neural Tube Defects\u2010An In Silico to Clinical Approach in West Bengal, India"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0269-6035","authenticated-orcid":false,"given":"Nirvika","family":"Paul","sequence":"first","affiliation":[{"name":"Department of Zoology University of Calcutta  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3773-066X","authenticated-orcid":false,"given":"Susanta","family":"Sadhukhan","sequence":"additional","affiliation":[{"name":"Department of Zoology University of Calcutta  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-6491","authenticated-orcid":false,"given":"Srilagna","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Zoology University of Calcutta  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4110-0297","authenticated-orcid":false,"given":"Anwesha","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Zoology University of Calcutta  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinesh","family":"Munian","sequence":"additional","affiliation":[{"name":"Department of Neonatology Institute of Postgraduate Medical Education &amp; Research  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-0115","authenticated-orcid":false,"given":"Kausik","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Calcutta  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0540-2597","authenticated-orcid":false,"given":"Biswabandhu","family":"Bankura","sequence":"additional","affiliation":[{"name":"Multidisciplinary Research Unit Medical College Kolkata  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8423-3228","authenticated-orcid":false,"given":"Krishnendu","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Carver College of Medicine University of Iowa  Iowa City USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9393-3173","authenticated-orcid":false,"given":"Sudakshina","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Zoology Vidyasagar College for Women  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3748-892X","authenticated-orcid":false,"given":"Madhusudan","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Zoology University of Calcutta  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3181c2bde8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1203\/pdr.0b013e3181f1ca99"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg0720s76"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0118961"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113308"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1415227"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.137323.112"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2015.01.002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25794"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl423"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2012.2096"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2008.01.005"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv195"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046688"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000096735"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530210052030"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e3181d22757"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2003\u201009.2009"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010020\u201002183\u20101"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010neuro\u2010062012\u2010170354"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150181505"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1167"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010023\u201001554\u20101"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23578"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2012.763"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032\u2010020\u201000161\u20102"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.85.3.6480"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604689"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20686"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh013"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr087"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.2145"},{"issue":"1","key":"e_1_2_10_35_1","first-page":"88","article-title":"The Relation Between Human Fetal Growth and Fetal Blood Levels of Insulin\u2010Like Growth Factors I and II, Their Binding Proteins, and Receptors","volume":"84","author":"Reece E. 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