{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:22:45Z","timestamp":1785777765488,"version":"3.56.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,6,7]],"date-time":"2012-06-07T00:00:00Z","timestamp":1339027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Clubfoot is a common birth defect characterized by inward posturing and rigid downward displacement of one or both feet. The etiology of syndromic forms of clubfoot is varied and the causes of isolated clubfoot are not well understood. A microduplication of 2.2\u2009Mb on chromosome 17q23.1q23.2 which includes T\u2010box 4 (<jats:italic>TBX4<\/jats:italic>), a hindlimb\u2010specific gene, and 16 other genes was recently identified in 3 of 66 families reported as nonsyndromic clubfoot, but additional non\u2010foot malformations place them in the syndromic clubfoot category. Our study assesses whether variation in or around <jats:italic>TBX4<\/jats:italic> contributes to nonsyndromic clubfoot. To determine whether this microduplication was a common cause of nonsyndromic clubfoot, 605 probands (from 148 multiplex and 457 simplex families) with nonsyndromic clubfoot were evaluated by copy number and oligonucleotide array CGH testing modalities. Only one multiplex family (0.68%) that had 16 with clubfoot and 9 with other foot anomalies, had a 350\u2009kb microduplication, which included the complete duplication of <jats:italic>TBX4<\/jats:italic> and <jats:italic>NACA2<\/jats:italic> and partial duplication of <jats:italic>BRIP1<\/jats:italic>. The microduplication was transmitted in an autosomal dominant pattern and all with the microduplication had a range of phenotypes from short wide feet and toes to bilateral clubfoot. Minimal evidence was found for an association between <jats:italic>TBX4<\/jats:italic> and clubfoot and no pathogenic sequence variants were identified in the two known <jats:italic>TBX4<\/jats:italic> hindlimb enhancer elements. Altogether, these results demonstrate that variation in and around the <jats:italic>TBX4<\/jats:italic> gene and the 17q23.1q23.2 microduplication are not a frequent cause of this common orthopedic birth defect and narrows the 17q23.1q23.2 nonsyndromic clubfoot\u2010associated region. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35418","type":"journal-article","created":{"date-parts":[[2012,6,7]],"date-time":"2012-06-07T20:16:07Z","timestamp":1339100167000},"page":"1620-1627","source":"Crossref","is-referenced-by-count":36,"title":["Studies of <i>TBX4<\/i> and chromosome 17q23.1q23.2: An uncommon cause of nonsyndromic 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