{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T20:36:45Z","timestamp":1773175005547,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,11]],"date-time":"2015-12-11T00:00:00Z","timestamp":1449792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Campomelic dysplasia and acampomelic campomelic dysplasia (ACD) are allelic disorders due to heterozygous mutations in or around <jats:italic>SOX9<\/jats:italic>. Translocations and deletions involving the <jats:italic>SOX9<\/jats:italic> 5\u2032 regulatory region are rare causes of these disorders, as well as Pierre Robin sequence (PRS) and 46,XY gonadal dysgenesis. Genotype\u2013phenotype correlations are not straightforward due to the complex epigenetic regulation of <jats:italic>SOX9<\/jats:italic> expression during development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report a three\u2010generation pedigree with a novel \u223c1 Mb deletion upstream of <jats:italic>SOX9<\/jats:italic> and including <jats:italic>KCNJ2<\/jats:italic> and <jats:italic>KCNJ16<\/jats:italic>, and ascertained for dominant transmission of PRS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Further characterization of the family identified subtle appendicular anomalies and a variable constellation of axial skeletal features evocative of ACD in several members. Affected males showed learning disability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The identified deletion was smaller than all other chromosome rearrangements associated with ACD. Comparison with other reported translocations and deletions involving this region allowed further refining of genotype\u2013phenotype correlations and an update of the smallest regions of overlap associated with the different phenotypes. Intrafamilial variability in this pedigree suggests a phenotypic continuity between ACD and PRS in patients carrying mutations in the <jats:italic>SOX9<\/jats:italic> 5\u2032 regulatory region. <jats:italic>Birth Defects Research (Part A) 106:61\u201368, 2016<\/jats:italic>. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23463","type":"journal-article","created":{"date-parts":[[2015,12,13]],"date-time":"2015-12-13T10:05:25Z","timestamp":1450001125000},"page":"61-68","source":"Crossref","is-referenced-by-count":16,"title":["Variability in a three\u2010generation family with pierre robin sequence, acampomelic campomelic dysplasia, and intellectual disability due to a novel \u223c1 Mb deletion upstream of <i>SOX9<\/i>, and including <i>KCNJ2<\/i> and <i>KCNJ16<\/i>"],"prefix":"10.1002","volume":"106","author":[{"given":"Marco","family":"Castori","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Molecular Medicine Sapienza University, San Camillo\u2010Forlanini Hospital Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Bottillo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Molecular Medicine Sapienza University, San Camillo\u2010Forlanini Hospital Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Morlino","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Molecular Medicine Sapienza University, San Camillo\u2010Forlanini Hospital Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Barone","sequence":"additional","affiliation":[{"name":"Center for Genetic Counseling and Reproductive Teratology, Maternal and Child Health Department Garibaldi Nesima Hospital Catania 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