{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:23:47Z","timestamp":1790601827875,"version":"4.1.0"},"reference-count":11,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T00:00:00Z","timestamp":1493251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:label\/><jats:p>DNMT3A\u2010Overgrowth Syndrome (also known as Tatton\u2013Brown\u2013Rahman Syndrome) (MIM 615879) has recently been described in 13 individuals with de novo heterozygous mutations in <jats:italic>DNMT3A<\/jats:italic> gene. This autosomal dominant condition is characterized by overgrowth, dysmorphic facial features and moderate intellectual disability. Missense and truncating point mutations, a small in\u2010frame deletion, as well as microdeletion 2p23 have been reported. Moreover, <jats:italic>DNMT3A<\/jats:italic> is commonly somatically mutated in acute myeloid leukemia. We herein report a family with two siblings and their father affected by the syndrome. The proband is a 12 year\u2010old boy with tall stature, macrocephaly, facial dysmorphism, and intellectual disability. His 10\u2010year\u2010old sister also has learning difficulties, overgrowth and mild facial dysmorphism. Their father is a 49 year\u2010old man with tall stature, macrocephaly, learning difficulties, and minor facial dysmorphism. He had a right occipital osteoma removed at 20 years of age. A heterozygous splice site mutation NM_022552.4 (<jats:italic>DNMT3A<\/jats:italic>): c.2323\u20102A\u2009&gt;\u2009T was found in the proband by whole exome sequencing analysis and by targeted Sanger Sequencing for the proband's sister and father. This mutation has not been previously reported and is believed to be pathogenic. Indeed, this substitution involves a highly conserved canonical splice site and is predicted to cause exon skipping. This is the first report of a familial transmission of <jats:italic>DNMT3A<\/jats:italic>\u2010Overgrowth Syndrome, supporting the autosomal dominant inheritance. The proband's phenotype is more severe than that of his two other affected family members, which illustrates variable expressivity in the syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38119","type":"journal-article","created":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T22:04:25Z","timestamp":1493330665000},"page":"1887-1890","source":"Crossref","is-referenced-by-count":21,"title":["A case of familial transmission of the newly described <i>DNMT3A<\/i>\u2010Overgrowth Syndrome"],"prefix":"10.1002","volume":"173","author":[{"given":"Gabrielle","family":"Lemire","sequence":"first","affiliation":[{"name":"D\u00e9partement de p\u00e9diatrie Service de g\u00e9n\u00e9tique m\u00e9dicale Centre Hospitalier Universitaire Ste\u2010Justine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Gauthier","sequence":"additional","affiliation":[{"name":"D\u00e9partement de p\u00e9diatrie Service de g\u00e9n\u00e9tique m\u00e9dicale Centre Hospitalier Universitaire Ste\u2010Justine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Fran\u00e7ois","family":"Soucy","sequence":"additional","affiliation":[{"name":"D\u00e9partement de p\u00e9diatrie Service de g\u00e9n\u00e9tique m\u00e9dicale Centre Hospitalier Universitaire Ste\u2010Justine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Ange","family":"Delrue","sequence":"additional","affiliation":[{"name":"D\u00e9partement de p\u00e9diatrie Service de g\u00e9n\u00e9tique m\u00e9dicale Centre Hospitalier Universitaire Ste\u2010Justine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)60702-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1271-x"},{"key":"e_1_2_7_4_1","unstructured":"Broad Institute. 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