{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T23:49:48Z","timestamp":1777765788473,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Kleefstra syndrome (KS) is a rare autosomic dominant genetic disorder caused by <jats:italic>euchromatic histone methyltransferase 1<\/jats:italic> (<jats:italic>EHMT1<\/jats:italic>) alterations. Patients mainly present with moderate to severe intellectual disability, a severe delay in\/or absence of speech, autism spectrum disorder, childhood hypotonia, neuropsychiatric anomalies, and distinctive dysmorphic features. Here, we report the cases of a male and a female, two younger siblings of three, with asymptomatic parents. An <jats:italic>EHMT1<\/jats:italic> new mutation was identified. Both presented with a typical core phenotype. Some specific features were noted, such as macrocephaly (previously reported) and enuresis (not yet described). Parental analysis identified the mutation in the mosaic state in the father. Reverse phenotyping enabled us to highlight the pauci phenotype features of inguinal hernia, azoospermia, and possible behavioral disorders. This allowed us to adapt his follow\u2010up and genetic counseling for the family. Our three reported cases provide a new description of KS with an intragenic <jats:italic>EHMT1<\/jats:italic> mutation, whereas in the literature most reported cases have <jats:italic>EHMT1<\/jats:italic> deletions. Moreover, in the areas of next\u2010generation sequencing and trio techniques with parental segregation, it is important to remain cautious about disregarding variants based on an autosomal recessive hypothesis.<\/jats:p>","DOI":"10.1002\/ajmg.a.62448","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T15:58:57Z","timestamp":1628265537000},"page":"3877-3883","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Kleefstra syndrome: Recurrence in siblings due to a paternal mosaic mutation"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4490-8224","authenticated-orcid":false,"given":"Florence","family":"Jobic","sequence":"first","affiliation":[{"name":"Reference Center for Rare Diseases Amiens\u2010Picardy University Hospital  Amiens France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1427-3910","authenticated-orcid":false,"given":"Emilie","family":"Lacot\u2010Leriche","sequence":"additional","affiliation":[{"name":"Reference Center for Rare Diseases Amiens\u2010Picardy University Hospital  Amiens France"},{"name":"EA 7273 CRP\u2010CPO University of Picardy, Jules Verne  Amiens France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0408-7468","authenticated-orcid":false,"given":"Am\u00e9lie","family":"Piton","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Diagnosis Institut de G\u00e9n\u00e9tique M\u00e9dicale d'Alsace, H\u00f4pitaux Universitaires de Strasbourg  Strasbourg France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Ga\u00eblle","family":"Le Moing","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Amiens\u2010Picardy University Hospital  Amiens France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4939-5608","authenticated-orcid":false,"given":"Mich\u00e8le","family":"Mathieu\u2010Dramard","sequence":"additional","affiliation":[{"name":"Reference Center for Rare Diseases Amiens\u2010Picardy University Hospital  Amiens France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Costantini","sequence":"additional","affiliation":[{"name":"Reference Center for Rare Diseases Amiens\u2010Picardy University Hospital  Amiens France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4428-6218","authenticated-orcid":false,"given":"Gilles","family":"Morin","sequence":"additional","affiliation":[{"name":"Genetics Laboratory Amiens\u2010Picardy University Hospital  Amiens France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5704-6830","authenticated-orcid":false,"given":"Guillaume","family":"Jedraszak","sequence":"additional","affiliation":[{"name":"Genetics Laboratory Amiens\u2010Picardy University Hospital  Amiens France"},{"name":"EA 4666 HEMATIM \u2013 CURS University of Picardy, Jules Verne  Amiens France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"issue":"4","key":"e_1_2_10_2_1","first-page":"431","article-title":"Twins with Kleefstra syndrome due to chromosome 9q34.3 microdeletion","volume":"26","author":"Atik T.","year":"2015","journal-title":"Genetic Counseling (Geneva, Switzerland)"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13764"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000494532"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.4.300"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-018-0193-9"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13039-016-0231-2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.04.005"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/505693"},{"key":"e_1_2_10_10_1","first-page":"1993","volume-title":"GeneReviews\u00ae","author":"Kleefstra T.","year":"2010"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028464"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.062950"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep35756","article-title":"Euchromatin histone methyltransferase 1 regulates cortical neuronal network development","volume":"6","author":"Martens M. 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