{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:21:52Z","timestamp":1790814112557,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education (MOHE) Malaysia","doi-asserted-by":"publisher","award":["FRGS\/1\/2019\/SKK08\/UM\/02\/17 (FP090-2019A)"],"award-info":[{"award-number":["FRGS\/1\/2019\/SKK08\/UM\/02\/17 (FP090-2019A)"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education (MOHE) Malaysia","doi-asserted-by":"publisher","award":["FRGS\/1\/2019\/SKK06\/UKM\/02\/06"],"award-info":[{"award-number":["FRGS\/1\/2019\/SKK06\/UKM\/02\/06"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Neural tube defects (NTDs) are common birth defects with a complex genetic etiology. Mouse genetic models have indicated a number of candidate genes, of which functional mutations in some have been found in human NTDs, usually in a heterozygous state. This study focuses on Ephs-ephrins as candidate genes of interest owing to growing evidence of the role of this gene family during neural tube closure in mouse models. Eph-ephrin genes were analyzed in 31 Malaysian individuals comprising seven individuals with sporadic spina bifida, 13 parents, one twin-sibling and 10 unrelated controls. Whole exome sequencing analysis and bioinformatic analysis were performed to identify variants in 22 known Eph-ephrin genes. We reported that three out of seven spina bifida probands and three out of thirteen family members carried a variant in either EPHA2 (rs147977279), EPHB6 (rs780569137) or EFNB1 (rs772228172). Analysis of public databases shows that these variants are rare. In exome datasets of the probands and parents of the probands with Eph-ephrin variants, the genotypes of spina bifida-related genes were compared to investigate the probability of the gene\u2013gene interaction in relation to environmental risk factors. We report the presence of Eph-ephrin gene variants that are prevalent in a small cohort of spina bifida patients in Malaysian families.<\/jats:p>","DOI":"10.3390\/genes13060952","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T08:50:22Z","timestamp":1653555022000},"page":"952","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Eph and Ephrin Variants in Malaysian Neural Tube Defect Families"],"prefix":"10.3390","volume":"13","author":[{"given":"Siti Waheeda","family":"Mohd-Zin","sequence":"first","affiliation":[{"name":"Invertebrate and Vertebrate Neurobiology Laboratory, Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia Cheng Wei","family":"Tan","sequence":"additional","affiliation":[{"name":"Invertebrate and Vertebrate Neurobiology Laboratory, Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wahib M.","family":"Atroosh","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7288-7910","authenticated-orcid":false,"given":"Meow-Keong","family":"Thong","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abu Bakar","family":"Azizi","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4170-5248","authenticated-orcid":false,"given":"Nicholas D. E.","family":"Greene","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2447-3211","authenticated-orcid":false,"given":"Noraishah Mydin","family":"Abdul-Aziz","sequence":"additional","affiliation":[{"name":"Invertebrate and Vertebrate Neurobiology Laboratory, Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1242\/dev.145904","article-title":"Neural tube closure: Cellular, molecular and biomechanical mechanisms","volume":"144","author":"Nikolopoulou","year":"2017","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1146\/annurev-neuro-062012-170354","article-title":"Neural tube defects","volume":"37","author":"Greene","year":"2014","journal-title":"Ann. 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