{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:00:44Z","timestamp":1790006444661,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T00:00:00Z","timestamp":1553731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nonsyndromic cleft lip and\/or palate is one of the most common human birth defects worldwide that affects the lip and\/or palate. The incidence of clefts varies among populations through ethnic, race, or geographical differences. The focus on Malay nonsyndromic cleft lip and\/or palate (NSCL\/P) is because of a scarce report on genetic study in relation to this deformity in Malaysia. We are interested to discuss about the genes that are susceptible to cause orofacial cleft formation in the family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genome\u2010wide linkage analysis was carried out on eight large extended families of NSCL\/P with the total of 91 individuals among Malay population using microarray platform. Based on linkage analyses findings, copy number variation (CNV) of <jats:italic>LPHN2<\/jats:italic>, <jats:italic>SATB2<\/jats:italic>, <jats:italic>PVRL3<\/jats:italic>, <jats:italic>COL21A1,<\/jats:italic> and <jats:italic>TOX3<\/jats:italic> were identified in four large extended families that showed linkage evidence using quantitative polymerase chain reaction (qPCR) as for a validation purpose. Copy number calculated (CNC) for each genes were determined with Applied Biosystems CopyCallerTM Software v2.0. Normal CNC of the target sequence expected was set at two.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genome\u2010wide linkage analysis had discovered several genes including <jats:italic>TOX3<\/jats:italic> and <jats:italic>COL21A1<\/jats:italic> in four different loci 4p15.2\u2010p16.1, 6p11.2\u2010p12.3, 14q13\u2010q21, and 16q12.1. There was significant decreased, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05 of <jats:italic>SATB2<\/jats:italic>, <jats:italic>COL21A1, <\/jats:italic>and <jats:italic>TOX3<\/jats:italic> copy number in extended families compared to the normal controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Novel linkage evidence and significant low copy number of <jats:italic>COL21A1 <\/jats:italic>and <jats:italic>TOX3 <\/jats:italic>in NSCLP family was confirmed. These genes increased the risks toward NSCLP formation in that family traits.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.635","type":"journal-article","created":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T04:10:37Z","timestamp":1553832637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Two novel genes <i>TOX3<\/i> and <i>COL21A1<\/i> in large extended Malay families with nonsyndromic cleft lip and\/or palate"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-9962","authenticated-orcid":false,"given":"Nurul Syazana","family":"Mohamad Shah","sequence":"first","affiliation":[{"name":"Reconstructive Science Unit, School of Medical Sciences Universiti Sains Malaysia Kubang Kerian Kelantan Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Sulong","sequence":"additional","affiliation":[{"name":"Human Genome Centre, School of Medical Sciences Universiti Sains Malaysia Kubang Kerian Kelantan Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Azman","family":"Wan Sulaiman","sequence":"additional","affiliation":[{"name":"Reconstructive Science Unit, School of Medical Sciences Universiti Sains Malaysia Kubang Kerian Kelantan Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Sukari","family":"Halim","sequence":"additional","affiliation":[{"name":"Hospital Universiti Sains Malaysia Kubang Kerian Kelantan Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1283-6"},{"issue":"211","key":"e_1_2_7_3_1","first-page":"2","article-title":"Oculo\u2010Auriculo\u2010vertebral spectrum: A review of the literature","volume":"5","author":"Beleza\u2010Meireles A.","year":"2014","journal-title":"Journal of Genetic Syndromes and Genetic Therapy"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/302041"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/302498"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/508214"},{"key":"e_1_2_7_7_1","article-title":"Genomic analyses in african populations identify novel risk loci for cleft palate","author":"Butali A.","year":"2018","journal-title":"Human Molecular Genetics"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1063"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.30.10.828"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20639"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33580"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2002.6712"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1597\/05-167"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00273010"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02754-5"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg248"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti571"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074102"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005385"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.12.017"},{"issue":"13","key":"e_1_2_7_21_1","first-page":"2862","article-title":"A multi\u2010ethnic genome\u2010wide association study identifies novel loci for non\u2010syndromic cleft lip with or without cleft palate on 2p24. 2, 17q23 and 19q13","volume":"25","author":"Leslie E. 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