{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:35:24Z","timestamp":1776274524692,"version":"3.50.1"},"reference-count":9,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FEDER programs"],"award-info":[{"award-number":["FEDER programs"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016913","name":"MSDAVENIR","doi-asserted-by":"publisher","award":["Devo\u2010Decode project"],"award-info":[{"award-number":["Devo\u2010Decode project"]}],"id":[{"id":"10.13039\/100016913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201010\u2010IAHU\u201001"],"award-info":[{"award-number":["ANR\u201010\u2010IAHU\u201001"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Loss\u2010of\u2010function variants in <jats:italic>KMT2D<\/jats:italic> are responsible for Kabuki syndrome type 1 (KS1). In the last 5\u2009years, missense variants in exon 38 or 39 in <jats:italic>KMT2D<\/jats:italic> have been found in patients exhibiting a new phenotype with multiple malformations and absence of intellectual disability, distinct from KS1. To date, only 16 cases have been reported with classic features of hearing loss, abnormality of the ear, lacrimal duct defects, branchial sinus\/neck pits, choanal atresia (CA), athelia, hypo(para)thyroidism, growth delay, and dental anomalies. We report here two families and one unpublished variant, refining the clinical and molecular knowledge on this new entity. Family 1 presented with apparently isolated autosomal dominant choanal atresia, in eight members across three generations. Exome sequencing (ES) in the proband and one cousin revealed a p.Glu3569Gly variant in exon 38 of <jats:italic>KMT2D<\/jats:italic>, segregating with choanal atresia in the family. Clinical reevaluation evidenced thyroid dysfunction, mild hearing anomalies, and hypoplastic nipple in some patients. Family 2 presented with nasolacrimal duct obstruction, hearing loss, mild facial features, unilateral axial polydactyly, and unilateral toe V\u2010VI syndactyly. ES revealed a de novo already reported p.Arg3582Gln variant in exon 38 of <jats:italic>KMT2D<\/jats:italic>. Considering these results and the existing literature, we suspect that missense variants in exon 38 of <jats:italic>KMT2D<\/jats:italic> are responsible for phenotypes that are even milder (isolated CA) and broader (polydactyly) than what has been previously described.<\/jats:p>","DOI":"10.1002\/ajmg.a.62642","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T11:56:58Z","timestamp":1642766218000},"page":"1600-1606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Refining the clinical phenotype associated with missense variants in exons 38 and 39 of <scp><i>KMT2D<\/i><\/scp>"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5565-3362","authenticated-orcid":false,"given":"Myl\u00e8ne","family":"Tharreau","sequence":"first","affiliation":[{"name":"UF Innovation en Diagnostic G\u00e9nomique des Maladies Rares, Laboratoire de G\u00e9n\u00e9tique Chromosomique Mol\u00e9culaire, FHU\u2010TRANSLAD Hospital Center University Dijon Bourgogne  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurore","family":"Garde","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs, FHU TRANSLAD Centre Hospitalier Universitaire Dijon  Dijon France"},{"name":"Genetics of Developmental Disorders Team INSERM \u2010 Bourgogne Franche\u2010Comt\u00e9 University, UMR 1231 GAD  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Marlin","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163 Imagine Institute, Universit\u00e9 de Paris  Paris France"},{"name":"Centre de R\u00e9f\u00e9rence \u00ab Surdit\u00e9s G\u00e9n\u00e9tiques \u00bb, F\u00e9d\u00e9ration de G\u00e9n\u00e9tique, H\u00f4pital Necker\u2010Enfants Malades Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Godelieve","family":"Morel","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163 Imagine Institute, Universit\u00e9 de Paris  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvain","family":"Ernest","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163 Imagine Institute, Universit\u00e9 de Paris  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Nambot","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs, FHU TRANSLAD Centre Hospitalier Universitaire Dijon  Dijon France"},{"name":"Genetics of Developmental Disorders Team INSERM \u2010 Bourgogne Franche\u2010Comt\u00e9 University, UMR 1231 GAD  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yannis","family":"Duffourd","sequence":"additional","affiliation":[{"name":"UF Innovation en Diagnostic G\u00e9nomique des Maladies Rares, Laboratoire de G\u00e9n\u00e9tique Chromosomique Mol\u00e9culaire, FHU\u2010TRANSLAD Hospital Center University Dijon Bourgogne  Dijon France"},{"name":"Genetics of Developmental Disorders Team INSERM \u2010 Bourgogne Franche\u2010Comt\u00e9 University, UMR 1231 GAD  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ninon","family":"Ternoy","sequence":"additional","affiliation":[{"name":"Service de N\u00e9onatologie, P\u00e9diatrie 2 Centre Hospitalier Universitaire  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Duvillard","sequence":"additional","affiliation":[{"name":"Service d'ORL Centre Hospitalier Universitaire  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8527-2210","authenticated-orcid":false,"given":"Siddharth","family":"Banka","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomics Medicine, St Mary's Hospital, Manchester University Hospital Foundation Trust  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Philippe","sequence":"additional","affiliation":[{"name":"UF Innovation en Diagnostic G\u00e9nomique des Maladies Rares, Laboratoire de G\u00e9n\u00e9tique Chromosomique Mol\u00e9culaire, FHU\u2010TRANSLAD Hospital Center University Dijon Bourgogne  Dijon France"},{"name":"Genetics of Developmental Disorders Team INSERM \u2010 Bourgogne Franche\u2010Comt\u00e9 University, UMR 1231 GAD  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christel","family":"Thauvin\u2010Robinet","sequence":"additional","affiliation":[{"name":"UF 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