{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:22:00Z","timestamp":1786972920644,"version":"build-2736575974"},"reference-count":7,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,12,28]],"date-time":"2019-12-28T00:00:00Z","timestamp":1577491200000},"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":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The non\u2010POU domain containing, octamer\u2010binding gene, <jats:italic>NONO<\/jats:italic>, is located on chromosome Xq13.1 and encodes a member of a small family of RNA and DNA binding proteins that perform a variety of tasks involved in RNA synthesis, transcriptional regulation and DNA repair. Hemizygous loss\u2010of\u2010function variants in <jats:italic>NONO<\/jats:italic> have been shown to cause mental retardation, X\u2010linked, syndromic 34 in males. Features of this disorder can include a range of neurodevelopmental phenotypes, left ventricular noncompaction (LVNC), congenital heart defects, and CNS anomalies. To date only eight cases have been described in the literature. Here we report two unrelated patients and a miscarried fetus with loss\u2010of\u2010function variants in <jats:italic>NONO<\/jats:italic>. Their phenotypes, and a review of previously reported cases, demonstrate that hemizygous loss\u2010of\u2010function variants in <jats:italic>NONO<\/jats:italic> cause a recognizable genetic syndrome. The cardinal features of this condition include developmental delay, intellectual disability, hypotonia, macrocephaly, structural abnormalities affecting the corpus callosum and\/or cerebellum, LVNC, congenital heart defects, and gastrointestinal\/feeding issues. This syndrome also carries an increased risk for strabismus and cryptorchidism and is associated with dysmorphic features that include an elongated face, up\/down\u2010slanted palpebral fissures, frontal bossing, and malar hypoplasia.<\/jats:p>","DOI":"10.1002\/ajmg.a.61466","type":"journal-article","created":{"date-parts":[[2019,12,28]],"date-time":"2019-12-28T10:45:38Z","timestamp":1577529938000},"page":"652-658","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Further delineation of the phenotypic spectrum associated with hemizygous loss\u2010of\u2010function variants in <i>NONO<\/i>"],"prefix":"10.1002","volume":"182","author":[{"given":"Maham","family":"Sewani","sequence":"first","affiliation":[{"name":"Texas Children's Hospital  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Nugent","sequence":"additional","affiliation":[{"name":"Children's Hospital of San Antonio  San Antonio Texas"},{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"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":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Tarnowski","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Hernandez\u2010Garcia","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Amiel","sequence":"additional","affiliation":[{"name":"1INSERM UMR 1163, Institut Imagine  Paris France"},{"name":"Universit\u00e9 Paris Descartes\u2010Sorbonne Paris Cit\u00e9, Institut Imagine  Paris France"},{"name":"Service de G\u00e9n\u00e9tique, H\u00f4pital Necker\u2010Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Whalen","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Fonctionnelle de g\u00e9n\u00e9tique clinique H\u00f4pital Armand Trousseau, Assistance publique\u2010H\u00f4pitaux de Paris, Centre de R\u00e9f\u00e9rence Maladies Rares des anomalies du d\u00e9veloppement et syndromes malformatifs  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Keren","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re, Assistance Publique\u2010H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Courtin","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re, Assistance Publique\u2010H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc C.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota"},{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Pichurin","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota"},{"name":"Center for Individualized Medicine Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"McLean","sequence":"additional","affiliation":[{"name":"Children's Hospital of San Antonio  San Antonio Texas"},{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1460-5169","authenticated-orcid":false,"given":"Daryl A.","family":"Scott","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"},{"name":"Department of Molecular Physiology and Biophysics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61091"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/21.17.4085"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4169"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050553"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.72"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-104039"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(74)80753-5"}],"container-title":["American Journal of 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