{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:28:05Z","timestamp":1773034085537,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Split Hand-Foot Malformation (SHFM) is a congenital limb defect characterized by a median cleft of the hands and\/or feet due to the absence\/hypoplasia of the central rays. It may occur as part of a syndromic condition or as an isolated malformation. The most common of the six genetic loci identified for this condition is correlated to SHFM1 and maps in the 7q21q22 region. SHFM1 is characterized by autosomal dominant transmission, incomplete penetrance and variable expressivity. Associated features often include hearing loss, intellectual disability\/developmental delay and craniofacial abnormalities. Disruption of the DLX5\/DLX6 genes, mapping within the SHFM1 locus, is now known to be responsible for the phenotype. Through SNP array, we analyzed a patient affected by SHFM1 associated with deafness and an abnormality of the inner ear (incomplete partition type I); we identified a deletion in 7q21, not involving the DLX5\/6 genes, but including exons 15 and 17 of DYNC1I1, known to act as exonic enhancers (eExons) of the DLX5\/6 genes. We further demonstrated the role of DYNC1I1 eExons in regulating DLX5\/6 expression by means of showing a reduced expression of the DLX5\/6 genes through RT-PCR in a patient-derived lymphoblastoid cell line. Furthermore, our data and a review of published cases do not support the hypothesis that DLX5\/6 are imprinted in humans. This work is an example of how the disruption of regulatory elements can be responsible for congenital malformations.<\/jats:p>","DOI":"10.3390\/genes14081526","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T01:50:37Z","timestamp":1690422637000},"page":"1526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Split Hand-Foot and Deafness in a Patient with 7q21.13-q21.3 Deletion Not Including the DLX5\/6 Genes"],"prefix":"10.3390","volume":"14","author":[{"given":"Irene","family":"Ambrosetti","sequence":"first","affiliation":[{"name":"Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Clinical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3554-2817","authenticated-orcid":false,"given":"Laura","family":"Bernardini","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9865-0751","authenticated-orcid":false,"given":"Marzia","family":"Pollazzon","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Grazia","family":"Giuffrida","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Guida","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0976-1258","authenticated-orcid":false,"given":"Francesca","family":"Peluso","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Chiara","family":"Baroni","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Clinical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Polizzi","sequence":"additional","affiliation":[{"name":"Department of Audiology, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0434-4172","authenticated-orcid":false,"given":"Manuela","family":"Napoli","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simonetta","family":"Rosato","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Trimarchi","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Gelmini","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-7854","authenticated-orcid":false,"given":"Stefano Giuseppe","family":"Caraffi","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Wischmeijer","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"},{"name":"Clinical Genetics Service and Coordination Center for Rare Diseases, Department of Pediatrics, Regional Hospital of Bolzano, 39100 Bolzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Frattini","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Azienda AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-4297","authenticated-orcid":false,"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia","family":"Garavelli","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"51R","DOI":"10.1093\/hmg\/ddg090","article-title":"Pathogenesis of split-hand\/split-foot malformation","volume":"12","author":"Duijf","year":"2003","journal-title":"Hum. 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