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Clubfoot or congenital talipes equinovarus (CTEV) is a three\u2010dimensional abnormality of the leg, ankle, and feet that leads to the anomalous positioning of foot and ankle joints and has an incidence of 1 per 1000 live births. OFCs and CTEV may occur together or separately in certain genetic syndromes in addition to other congenital abnormalities. Here, we sought to decipher the genetic etiology of OFC and CTEV that occurred together in six probands.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>At the time of recruitment, the most clinically obvious congenital anomalies in these individuals were the OFC and CTEV. We carried out whole\u2010exome sequencing (WES) on DNA samples from probands and available parents employing the Agilent SureSelect XT kit and Illumina HiSeq2500 platform, followed by bioinformatics analyses. WES variants were validated by clinical Sanger Sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the six probands, we observed probable pathogenic genetic variants in four. In three probands with probable pathogenic genetic variants, each individual had variants in three different genes, whereas one proband had probable pathogenic variant in just one gene. In one proband, we observed variants in <jats:italic>DIS3L2<\/jats:italic>, a gene associated with Perlman syndrome. A second proband had variants in <jats:italic>EPG5<\/jats:italic> (associated with Vici Syndrome), <jats:italic>BARX1<\/jats:italic> and <jats:italic>MKI67<\/jats:italic>, while another proband had potentially etiologic variants in <jats:italic>FRAS1<\/jats:italic> (associated with Fraser Syndrome 1), <jats:italic>TCOF1<\/jats:italic> (associated with Treacher Collins Syndrome 1) and <jats:italic>MKI67<\/jats:italic>. The last proband had variants in <jats:italic>FRAS1<\/jats:italic>, <jats:italic>PRDM16<\/jats:italic> (associated with Cardiomyopathy, dilated, 1LL\/Left ventricular noncompaction 8) and <jats:italic>CHD7<\/jats:italic> (associated with CHARGE syndrome\/Hypogonadotropic hypogonadism 5 with or without anosmia).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that clubfoot and OFCs are two congenital abnormalities that can co\u2010occur in certain individuals with varying genetic causes and expressivity, warranting the need for deep phenotyping.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1655","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T07:00:19Z","timestamp":1615791619000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Co\u2010occurrence of orofacial clefts and clubfoot phenotypes in a sub\u2010Saharan African cohort: Whole\u2010exome sequencing implicates multiple syndromes and genes"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0080-9101","authenticated-orcid":false,"given":"Lord J. J.","family":"Gowans","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biotechnology Kwame Nkrumah University of Science and Technology Kumasi Ghana"},{"name":"Department of Oral and Maxillofacial Sciences Dental School Kwame Nkrumah University of Science and Technology Kumasi Ghana"},{"name":"Department of Oral Pathology, Radiology and Medicine University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura","family":"Al Dhaheri","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics John Hopkins University Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Busch","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon","family":"Obiri\u2010Yeboah","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Sciences Dental School Kwame Nkrumah University of Science and Technology Kumasi Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Oti","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Sciences Dental School Kwame Nkrumah University of Science and Technology Kumasi Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel K.","family":"Sabbah","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Child Oral Health Dental School Kwame Nkrumah University of Science and Technology Kumasi Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fareed K. N.","family":"Arthur","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology Kwame Nkrumah University of Science and Technology Kumasi Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waheed O.","family":"Awotoye","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9176-0221","authenticated-orcid":false,"given":"Azeez A.","family":"Alade","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Twumasi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology Kwame Nkrumah University of Science and Technology Kumasi Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pius","family":"Agbenorku","sequence":"additional","affiliation":[{"name":"Department of Surgery School of Medical Sciences Kwame Nkrumah University of Science and Technology Kumasi Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyikua","family":"Plange\u2010Rhule","sequence":"additional","affiliation":[{"name":"Department of Child Health School of Medical Sciences Kwame Nkrumah University of Science and Technology Kumasi Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thirona","family":"Naicker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of KwaZulu\u2010Natal South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Donkor","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Sciences Dental School Kwame Nkrumah University of Science and Technology Kumasi Ghana"},{"name":"Department of Surgery School of Medical Sciences Kwame Nkrumah University of Science and Technology Kumasi Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nara L. 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