{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:34:17Z","timestamp":1791286457643,"version":"4.1.0"},"reference-count":90,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2002,8,27]],"date-time":"2002-08-27T00:00:00Z","timestamp":1030406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[2002,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>HOX<\/jats:italic> genes encode a family of transcription factors of fundamental importance for body patterning during embryonic development. Humans, like most vertebrates, have 39 <jats:italic>HOX<\/jats:italic> genes organized into four clusters, with major roles in the development of the central nervous system, axial skeleton, gastrointestinal and urogenital tracts, external genitalia, and limbs. The first two limb malformations shown to be caused by mutations in the human <jats:italic>HOX<\/jats:italic> genes were synpolydactyly and hand\u2010foot\u2010genital syndrome, which result from mutations in <jats:italic>HOXD13<\/jats:italic> and <jats:italic>HOXA13<\/jats:italic>, respectively. This review describes a variety of limb malformations now known to be caused by specific different mutations in these two genes, including polyalanine tract expansions, nonsense mutations, and missense mutations, many with phenotypic consequences that could not have been predicted from previous knowledge of mouse models or HOX protein function. Limb malformations may also result from chromosomal deletions involving the <jats:italic>HOXD<\/jats:italic> and <jats:italic>HOXA<\/jats:italic> clusters, and from regulatory mutations affecting single or multiple <jats:italic>HOX<\/jats:italic> genes. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.10776","type":"journal-article","created":{"date-parts":[[2002,10,9]],"date-time":"2002-10-09T05:01:24Z","timestamp":1034139684000},"page":"256-265","source":"Crossref","is-referenced-by-count":185,"title":["Limb malformations and the human <i>HOX<\/i> genes"],"prefix":"10.1002","volume":"112","author":[{"given":"Frances 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