{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:59:21Z","timestamp":1787061561522,"version":"build-2736575974"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:00:00Z","timestamp":1549497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT098051"],"award-info":[{"award-number":["WT098051"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003921","name":"Department of Health, Australian Government","doi-asserted-by":"publisher","award":["WT098051"],"award-info":[{"award-number":["WT098051"]}],"id":[{"id":"10.13039\/501100003921","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":[[2019,4]]},"abstract":"<jats:p>\n                    <jats:italic>DDX3X<\/jats:italic>\n                    (Xp11.4) encodes a DEAD\u2010box RNA helicase that escapes X chromosome inactivation. Pathogenic variants in\n                    <jats:italic>DDX3X<\/jats:italic>\n                    have been shown to cause X\u2010linked intellectual disability (ID) (MRX102, MIM: 300958). The phenotypes associated with\n                    <jats:italic>DDX3X<\/jats:italic>\n                    variants are heterogeneous and include brain and behavioral abnormalities, microcephaly, hypotonia, and movement disorders and\/or spasticity. The majority of\n                    <jats:italic>DDX3X<\/jats:italic>\n                    variants described are de novo mutations in females with ID. In contrast, most male\n                    <jats:italic>DDX3X<\/jats:italic>\n                    variants are inherited from an unaffected mother, with one documented exception being a recently identified de novo splice site variant. It has been suggested, therefore, that\n                    <jats:italic>DDX3X<\/jats:italic>\n                    exerts its effects through haploinsufficiency in females, and that affected males carry hypomorphic alleles that retain partial function. Given the lack of male de novo\n                    <jats:italic>DDX3X<\/jats:italic>\n                    variants, loss\u2010of\u2010function variants in this gene are suspected to be male lethal. Through whole\u2010exome sequencing, we identified three unrelated males with hemizygous missense\n                    <jats:italic>DDX3X<\/jats:italic>\n                    variants and ID. All three variants were confirmed by Sanger sequencing, with two established as de novo. In silico analyses were supportive of pathogenicity. We report the male phenotypes and compare them to phenotypes observed in previously reported male and female patients. In conclusion, we propose that de novo\n                    <jats:italic>DDX3X<\/jats:italic>\n                    variants are not necessarily male lethal and should be considered as a cause of syndromic ID in both males and females.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.61061","type":"journal-article","created":{"date-parts":[[2019,2,8]],"date-time":"2019-02-08T00:18:17Z","timestamp":1549585097000},"page":"570-578","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["De novo\n                    <i>DDX3X<\/i>\n                    missense variants in males appear viable and contribute to syndromic intellectual disability"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8641-3580","authenticated-orcid":false,"given":"Pantelis","family":"Nicola","sequence":"first","affiliation":[{"name":"University Hospital of South Manchester NHS Foundation Trust  Manchester United Kingdom"},{"name":"Manchester Centre for Genomic Medicine  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0658-1275","authenticated-orcid":false,"given":"Patrick R.","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic  Rochester Minnesota"},{"name":"Department of Health Sciences Research Mayo Clinic  Rochester Minnesota"},{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0705-1228","authenticated-orcid":false,"given":"Kristen J.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole L.","family":"Bertsch","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric W.","family":"Klee","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic  Rochester Minnesota"},{"name":"Department of Health Sciences Research Mayo Clinic  Rochester Minnesota"},{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota"},{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Hasadsri","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel N.","family":"Pichurin","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Rankin","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Royal Devon and Exeter NHS Foundation Trust  Exeter United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Lucy","family":"Raymond","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research University of Cambridge  Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"DDD Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Clayton\u2010Smith","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine  Manchester United Kingdom"},{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences University of Manchester  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2005.01.010"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004962"},{"issue":"14","key":"e_1_2_6_4_1","first-page":"2905","article-title":"Targeted inactivation of murine Ddx3x: Essential roles of Ddx3x in placentation and embryogenesis","volume":"25","author":"Chen C. 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