{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:07:50Z","timestamp":1789949270710,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,11,18]],"date-time":"2015-11-18T00:00:00Z","timestamp":1447804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG)"},{"name":"Berlin-Brandenburg School for Regenerative Therapies (BSRT)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:sec><jats:label\/><jats:p>Synpolydactyly (SPD) is a rare congenital limb disorder characterized by syndactyly between the third and fourth fingers and an additional digit in the syndactylous web. In most cases SPD is caused by heterozygous mutations in <jats:italic>HOXD13<\/jats:italic> resulting in the expansion of a N\u2010terminal polyalanine tract. If homozygous, the mutation results in severe shortening of all metacarpals and phalanges with a morphological transformation of metacarpals to carpals. Here, we describe a novel homozygous missense mutation in a family with unaffected consanguineous parents and severe brachydactyly and metacarpal\u2010to\u2010carpal transformation in the affected child. We performed whole exome sequencing on the index patient, followed by Sanger sequencing of parents and patient to investigate cosegregation. The DNA\u2010binding ability of the mutant protein was tested with electrophoretic mobility shift assays. We demonstrate that the c.938C&gt;G (p.313T&gt;R) mutation in the DNA\u2010binding domain of HOXD13 prevents binding to DNA in vitro. Our results show to our knowledge for the first time that a missense mutation in <jats:italic>HOXD13<\/jats:italic> underlies severe brachydactyly with metacarpal\u2010to\u2010carpal transformation. The mutation is non\u2010penetrant in heterozygous carriers. In conjunction with the literature we propose the possibility that the metacarpal\u2010to\u2010carpal transformation results from a homozygous loss of functional HOXD13 protein in humans in combination with an accumulation of non\u2010functional HOXD13 that might be able to interact with other transcription factors in the developing limb. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37464","type":"journal-article","created":{"date-parts":[[2015,11,19]],"date-time":"2015-11-19T03:25:07Z","timestamp":1447903507000},"page":"615-621","source":"Crossref","is-referenced-by-count":19,"title":["A homozygous HOXD13 missense mutation causes a severe form of synpolydactyly with metacarpal to carpal transformation"],"prefix":"10.1002","volume":"170","author":[{"given":"Daniel M.","family":"Ibrahim","sequence":"first","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naeimeh","family":"Tayebi","sequence":"additional","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexej","family":"Knaus","sequence":"additional","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asita C.","family":"Stiege","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afsaneh","family":"Sahebzamani","sequence":"additional","affiliation":[{"name":"Department of Genetic Welfare Organization Kerman Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Hecht","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Molecular Genetics Berlin Germany"},{"name":"Berlin Brandenburg Center for Regenerative Therapies Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Mundlos","sequence":"additional","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Max Planck Institute for Molecular Genetics Berlin Germany"},{"name":"Berlin\u2010Brandenburg School for Regenerative Therapies (BSRT) Berlin Germany"},{"name":"Berlin Brandenburg Center for Regenerative Therapies Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Spielmann","sequence":"additional","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Max Planck Institute for Molecular Genetics Berlin Germany"},{"name":"Berlin\u2010Brandenburg School for Regenerative Therapies (BSRT) Berlin 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