{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:39:53Z","timestamp":1787020793700,"version":"build-2736575974"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009702","name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico","doi-asserted-by":"publisher","award":["RC 2019-2020"],"award-info":[{"award-number":["RC 2019-2020"]}],"id":[{"id":"10.13039\/501100009702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009702","name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico","doi-asserted-by":"publisher","award":["PED-CARE-2018"],"award-info":[{"award-number":["PED-CARE-2018"]}],"id":[{"id":"10.13039\/501100009702","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ital J Pediatr"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      De novo pathogenic variants in the\n                      <jats:italic>DDX3X<\/jats:italic>\n                      gene are reported to account for 1\u20133% of unexplained intellectual disability (ID) in females, leading to the rare disease known as\n                      <jats:italic>DDX3X<\/jats:italic>\n                      syndrome (MRXSSB, OMIM #300958). Besides ID, these patients manifest a variable clinical presentation, which includes neurological and behavioral defects, and abnormal brain MRIs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report a 10-year-old girl affected by delayed psychomotor development, delayed myelination, and polymicrogyria (PMG). We identified a novel de novo missense mutation in the\n                      <jats:italic>DDX3X<\/jats:italic>\n                      gene (c.625C\u2009&gt;\u2009G) by whole exome sequencing (WES). The\n                      <jats:italic>DDX3X<\/jats:italic>\n                      gene encodes a DEAD-box ATP-dependent RNA-helicase broadly implicated in gene expression through regulation of mRNA metabolism. The identified mutation is located just upstream the helicase domain and is suggested to impair the protein activity, thus resulting in the altered translation of DDX3X-dependent mRNAs. The proband, presenting with the typical PMG phenotype related to the syndrome, does not show other clinical signs frequently reported in presence of missense\n                      <jats:italic>DDX3X<\/jats:italic>\n                      mutations that are associated with a most severe clinical presentation. In addition, she has brachycephaly, never described in female\n                      <jats:italic>DDX3X<\/jats:italic>\n                      patients, and macroglossia, that has never been associated with the syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This case expands the knowledge of\n                      <jats:italic>DDX3X<\/jats:italic>\n                      pathogenic variants and the associated\n                      <jats:italic>DDX3X<\/jats:italic>\n                      syndrome phenotypic spectrum.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13052-021-01033-4","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T06:03:18Z","timestamp":1617170598000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A novel de novo DDX3X missense variant in a female with brachycephaly and intellectual disability: a case report"],"prefix":"10.1186","volume":"47","author":[{"given":"Giada","family":"Moresco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jole","family":"Costanza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Santaniello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Rondinone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Grilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Prada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Orcesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Coro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pichiecchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Marchisio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Miozzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Milani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"issue":"2","key":"1033_CR1","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.ajhg.2015.07.004","volume":"97","author":"L Snijders Blok","year":"2015","unstructured":"Snijders Blok L, Madsen E, Juusola J, Gilissen C, Baralle D, Reijnders MRF, et al. Mutations in DDX3X are a common cause of unexplained intellectual disability with gender-specific effects on Wnt signaling. Am J Hum Genet. 2015;97(2):343\u201352. https:\/\/doi.org\/10.1016\/j.ajhg.2015.07.004.","journal-title":"Am J Hum Genet"},{"key":"1033_CR2","unstructured":"The DDX3X Foundation website. https:\/\/ddx3x.org\/about-ddx3x\/. Accessed 24 May 2020."},{"key":"1033_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40246-018-0141-y","volume":"12","author":"G Kellaris","year":"2018","unstructured":"Kellaris G, Khan K, Baig SM, Tsai IC, Zamora FM, Ruggieri P, et al. A hypomorphic inherited pathogenic variant in DDX3X causes male intellectual disability with additional neurodevelopmental and neurodegenerative features. 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