{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T10:43:18Z","timestamp":1769596998628,"version":"3.49.0"},"reference-count":15,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["grant # RC 2021 and 2022 to IRCCS Medea  and RC202"],"award-info":[{"award-number":["grant # RC 2021 and 2022 to IRCCS Medea  and RC202"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Septo-optic dysplasia (SOD) syndrome is a rare congenital disorder characterized by a classic triad of optic nerve\/chiasm hypoplasia, agenesis of septum pellucidum and corpus callosum, and hypoplasia of the hypothalamic-pituitary axis.<\/jats:p><jats:p>Herein, we report the clinical case of 2-year-old boy presenting with psychomotor delay, nystagmus, congenital hypothyroidism, and a clinically relevant growth delay. The neuroradiological examination showed partial segmental agenesis of the corpus callosum, agenesis of the septum pellucidum, optic nerve hypoplasia, and a small pituitary gland with a small median pituitary stalk. A whole-exome sequencing analysis detected a novel heterozygous de novo variant c.1069_1070delAG in SON, predicted as likely pathogenic.<\/jats:p><jats:p>To date, SON pathogenic variants have been described as responsible for Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, a multisystemic neurodevelopmental disorder mainly characterized by intellectual disability, facial dysmorphisms, visual abnormalities, brain malformations, feeding difficulties, and growth delay. The herein described case is the first recognized clinic-radiological occurrence of SOD syndrome with hypothalamic-pituitary dysfunction in a patient carrying a SON gene variant, considered responsible of ZTTK syndrome, suggesting a possible relationship between SOD and SON gene alterations, never described so far, making the search for SON gene mutations advisable in patients with SOD.<\/jats:p>","DOI":"10.1055\/a-2114-4387","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:31:35Z","timestamp":1687393895000},"page":"191-195","source":"Crossref","is-referenced-by-count":2,"title":["A Novel De novo Heterozygous Mutation in the SON Gene Associated with Septo-optic Dysplasia: A New Phenotype"],"prefix":"10.1055","volume":"55","author":[{"given":"Ludovica","family":"Pasca","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy"},{"name":"Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3795-1972","authenticated-orcid":false,"given":"Davide","family":"Politano","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy"},{"name":"Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Cavallini","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don C. Gnocchi, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Panzeri","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"Vigone","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, San Raffaele Hospital, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Baldoli","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Abbate","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, San Raffaele Hospital, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaia","family":"Kullmann","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Marelli","sequence":"additional","affiliation":[{"name":"Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Pozzobon","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, San Raffaele Hospital, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaia","family":"Vincenzi","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, San Raffaele Hospital, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Nacinovich","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Bassi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8709-6732","authenticated-orcid":false,"given":"Romina","family":"Romaniello","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"160.e1","DOI":"10.1016\/j.crad.2020.09.007","article-title":"Review of the MRI brain findings of septo-optic dysplasia","volume":"76","author":"D J Ward","year":"2021","journal-title":"Clin Radiol"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.beem.2010.06.008","article-title":"Septo-optic dysplasia and other midline defects: the role of transcription factors: HESX1 and beyond","volume":"25","author":"M J McCabe","year":"2011","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2147\/EB.S186307","article-title":"Neuro-ophthalmological manifestations of septo-optic dysplasia: current perspectives","volume":"11","author":"M Ganau","year":"2019","journal-title":"Eye Brain"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/B978-0-12-820683-6.00005-1","article-title":"Septo-optic dysplasia","volume":"181","author":"I Sataite","year":"2021","journal-title":"Handb Clin Neurol"},{"issue":"01","key":"ref5","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13041-020-00622-4","article-title":"Knockdown of Son, a mouse homologue of the ZTTK syndrome gene, causes neuronal migration defects and dendritic spine abnormalities","volume":"13","author":"M Ueda","year":"2020","journal-title":"Mol Brain"},{"issue":"12","key":"ref6","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.1002\/ajmg.a.62445","article-title":"ZTTK syndrome: clinical and molecular findings of 15 cases and a review of the literature","volume":"185","author":"S T Kushary","year":"2021","journal-title":"Am J Med Genet 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Miller","year":"2000","journal-title":"Neurology"},{"issue":"03","key":"ref10","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.ajhg.2016.06.029","article-title":"De novo mutations in SON disrupt RNA splicing of genes essential for brain development and metabolism, causing an intellectual-disability syndrome","volume":"99","author":"J H Kim","year":"2016","journal-title":"Am J Hum Genet"},{"issue":"10","key":"ref11","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/ncb2839","article-title":"SON connects the splicing-regulatory network with pluripotency in human embryonic stem cells","volume":"15","author":"X Lu","year":"2013","journal-title":"Nat Cell Biol"},{"issue":"7809","key":"ref12","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"K J Karczewski","year":"2020","journal-title":"Nature"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.molcel.2011.03.014","article-title":"SON controls cell-cycle progression by coordinated regulation of RNA splicing","volume":"42","author":"E-Y Ahn","year":"2011","journal-title":"Mol Cell"},{"issue":"10","key":"ref14","doi-asserted-by":"crossref","first-page":"e1432","DOI":"10.1002\/mgg3.1432","article-title":"Phenotypic expansion in Zhu-Tokita-Takenouchi-Kim syndrome caused by de novo variants in the SON gene","volume":"8","author":"R Slezak","year":"2020","journal-title":"Mol Genet Genomic Med"},{"issue":"03","key":"ref15","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41431-021-00960-4","article-title":"Establishing the phenotypic spectrum of ZTTK syndrome by analysis of 52 individuals with variants in SON","volume":"30","author":"A JM Dingemans","year":"2022","journal-title":"Eur J Hum Genet"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2114-4387.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T12:37:26Z","timestamp":1730810246000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2114-4387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,21]]},"references-count":15,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2024,5,6]]},"published-print":{"date-parts":[[2024,6]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2114-4387","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,6,21]]},"published":{"date-parts":[[2023,6,21]]}}}