{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:15:14Z","timestamp":1784042114846,"version":"3.55.0"},"reference-count":18,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,2,17]],"date-time":"2019-02-17T00:00:00Z","timestamp":1550361600000},"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":[[2019,5]]},"abstract":"<jats:p>The <jats:italic>NONO<\/jats:italic> gene encodes a nuclear protein involved in RNA metabolism. Hemizygous loss\u2010of\u2010function <jats:italic>NONO<\/jats:italic> variants have been associated with syndromic intellectual disability and with left ventricular noncompaction (LVNC). A two\u2010year\u2010old boy presented to the University of Utah's Penelope Undiagnosed Disease Program with developmental delay, nonfamilial features, relative macrocephaly, and dilated cardiomyopathy with LVNC and Ebstein anomaly. Brain MRI showed a thick corpus callosum, mild Chiari I malformation, and a flattened pituitary. Exome sequencing identified a novel intronic deletion (c.154+5_154+6delGT) in the <jats:italic>NONO<\/jats:italic> gene. Splicing studies demonstrated intron 4 read\u2010through and the use of an alternative donor causing the frameshift p.Asn52Serfs*6. Family segregation analysis showed that the variant occurred de novo in the boy's unaffected mother. MRI and endocrine findings suggest that hypopituitarism may contribute to growth failure, abnormal thyroid hormone levels, cryptorchidism, or delayed puberty in patients with <jats:italic>NONO<\/jats:italic>\u2010associated disease. Also, including this case LVNC has been observed in five out of eight patients, and this report also confirms an association between loss of <jats:italic>NONO<\/jats:italic> and Ebstein anomaly. In some cases, unrelated individuals share the same pathogenic <jats:italic>NONO<\/jats:italic> variants but do not all have clinically significant LVNC, suggesting that additional modifiers may contribute to cardiac phenotypes.<\/jats:p>","DOI":"10.1002\/ajmg.a.61091","type":"journal-article","created":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T05:06:16Z","timestamp":1550466376000},"page":"792-796","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Expanding the genetic and clinical spectrum of the NONO\u2010associated X\u2010linked intellectual disability syndrome"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2901-8610","authenticated-orcid":false,"given":"Colleen M.","family":"Carlston","sequence":"first","affiliation":[{"name":"Department of Pathology University of Utah  Salt Lake City Utah"},{"name":"ARUP Institute for Clinical and Experimental Pathology  Salt 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