{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:15:11Z","timestamp":1784042111489,"version":"3.55.0"},"reference-count":16,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RC2022"],"award-info":[{"award-number":["RC2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>NONO (Non-Pou Domain-Containing Octamer-Binding Protein) gene maps on chromosome Xq13.1 and hemizygous loss-of-function nucleotide variants are associated with an emerging syndromic form of intellectual developmental disorder (MRXS34; MIM #300967), characterized by developmental delay, intellectual disability, poor language, dysmorphic facial features, and microcephaly. Structural brain malformation, such as corpus callosum and cerebellar abnormalities, and heart defects, in particular left ventricular non-compaction (LVNC), represent the most recurrent congenital malformations, recorded both in about 80% of patients, and can be considered the distinctive imaging findings of this disorder. We present on a further case of NONO-related disease; prenatally diagnosed in a fetus with complete corpus callosum agenesis; absence of septum pellucidum; pericallosal artery; LVNC and Ebstein\u2019s anomaly. A high-resolution microarray analysis demonstrated the presence of a deletion affecting the NONO 3\u2032UTR; leading to a marked hypoexpression of the gene and the complete absence of the protein in cultured amniocytes. This case expands the mutational spectrum of MRXS34, advises to evaluate NONO variants in pre- and postnatal diagnosis of subjects affected by LVNC and other heart defects, especially if associated with corpus callosum anomalies and confirm that CNVs (Copy Number Variants) represent a non-negligible cause of Mendelian disorders.<\/jats:p>","DOI":"10.3390\/diagnostics12102354","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T20:58:47Z","timestamp":1664398727000},"page":"2354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["3\u2032UTR Deletion of NONO Leads to Corpus Callosum Anomaly, Left Ventricular Non-Compaction and Ebstein\u2019s Anomaly in a Male Fetus"],"prefix":"10.3390","volume":"12","author":[{"given":"Maria Grazia","family":"Giuffrida","sequence":"first","affiliation":[{"name":"Cytogenetics Unit, IRCCS Casa Sollievo della Sofferenza Foundation, Viale Cappuccini, snc, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Goldoni","sequence":"additional","affiliation":[{"name":"Cytogenetics Unit, IRCCS Casa Sollievo della Sofferenza Foundation, Viale Cappuccini, snc, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luce","family":"Genovesi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Carpentieri","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Ges\u00f9, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7007-7957","authenticated-orcid":false,"given":"Barbara","family":"Torres","sequence":"additional","affiliation":[{"name":"Cytogenetics Unit, IRCCS Casa Sollievo della Sofferenza Foundation, Viale Cappuccini, snc, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca Daniela","family":"Deac","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, AUSL Romagna, Infermi Hospital, 47923 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3601-176X","authenticated-orcid":false,"given":"Serena","family":"Cecchetti","sequence":"additional","affiliation":[{"name":"Core Facilities Confocal Microscopy Unit, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, AUSL Romagna, Infermi Hospital, 47923 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8413-621X","authenticated-orcid":false,"given":"Alessandro","family":"Vaisfeld","sequence":"additional","affiliation":[{"name":"Institute of Genomic Medicine, Catholic University School of Medicine, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6802-1356","authenticated-orcid":false,"given":"Elisabetta","family":"Flex","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3554-2817","authenticated-orcid":false,"given":"Laura","family":"Bernardini","sequence":"additional","affiliation":[{"name":"Cytogenetics Unit, IRCCS Casa Sollievo della Sofferenza Foundation, Viale Cappuccini, snc, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1038\/nn.4169","article-title":"Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects","volume":"18","author":"Mircsof","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1038\/ejhg.2016.72","article-title":"Intellectual disability and non-compaction cardiomyopathy with a de novo NONO mutation identified by exome sequencing","volume":"24","author":"Reinstein","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1136\/jmedgenet-2016-104039","article-title":"Congenital heart defects and left ventricular non-compaction in males with loss-of-function variants in NONO","volume":"54","author":"Scott","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/ajmg.a.61091","article-title":"Expanding the genetic and clinical spectrum of the NONO-associated X-linked intellectual disability syndrome","volume":"179","author":"Carlston","year":"2019","journal-title":"Am. J. Med. Genet. 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