{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:52:11Z","timestamp":1789667531073,"version":"4.0.1"},"reference-count":9,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T00:00:00Z","timestamp":1595548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Uniwersytet Medyczny im. Piast\u00f3w Slaskich we Wroclawiu","doi-asserted-by":"publisher","award":["SUB.E160.19.004"],"award-info":[{"award-number":["SUB.E160.19.004"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009687","name":"Uniwersytet Medyczny im. Piast\u00f3w Slaskich we Wroclawiu","doi-asserted-by":"publisher","award":["SUB.A290.19.020"],"award-info":[{"award-number":["SUB.A290.19.020"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The genetic etiology of intellectual and psychomotor disability without a defined spectrum of dysmorphic features is usually monogenic. As no diagnostic criteria for such diseases are established, the clinical diagnosis becomes to be a challenge. The object of our paper is to present two patients with non\u2010specific clinical symptoms for whom whole\u2010exome\u2010sequencing identified the new SON mutations and thus allowed for establishing the diagnosis of Zhu\u2010Tokita\u2010Takenouchi\u2010Kim (ZTTK) syndrome. In both patients, the same symptoms including hypotonia, developmental and speech delay, feeding difficulties as well as frequent infections of the respiratory tract and internal ear were observed. However, both cases presented also with exceptional symptoms such as in case 1 ventriculomegaly and asymmetry of ventricles, hypoplastic left heart syndrome (HLHS), intellectual disability, intestinal malrotation, gastroparesis, and duodenal atresia and in the case 2 febrile seizures and reduced IgA levels. We will be presenting the patients and comparing them to 30 previously described cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing (WES) was performed on the probands\u2019 DNA and paired\u2010end sequenced (2x100\u00a0bp) on HiSeq 1500. Variants considered as disease\u2010causing were validated in the proband and studied in all available family members by amplicon deep sequencing performed using Nextera XT Kit and sequenced on HiSeq 1500.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We have identified two new variants in SON gene. In case 1 it has been a heterozygous frameshift variant p.(Ala1340GlnfsTer26), while in case 2 it has been a heterozygous frameshift variant, p.(Asp1640GlyfsTer7). Both variants are described for the first time and up to now, are not mentioned in any database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As there are no precise criteria established for the clinical diagnosis of ZTTK, an identification of <jats:italic>SON<\/jats:italic> gene mutation by whole\u2010exome\u2010sequencing is the best method that allows for a diagnosis of this syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1432","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T08:53:21Z","timestamp":1595580801000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Phenotypic expansion in Zhu\u2010Tokita\u2010Takenouchi\u2010Kim syndrome caused by de novo variants in the <i>SON<\/i> gene"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6738-9565","authenticated-orcid":false,"given":"Ryszard","family":"Slezak","sequence":"first","affiliation":[{"name":"Department of Genetics Wroclaw Medical University Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Smigiel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Rare Disorders Wroclaw Medical University Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Rydzanicz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Pollak","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Kosinska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Stawinski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Malgorzata Sasiadek","sequence":"additional","affiliation":[{"name":"Department of Genetics Wroclaw Medical University Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-5526","authenticated-orcid":false,"given":"Rafal","family":"Ploski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.03.014"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13394"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.01.025"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.029"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37761"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.035"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.953"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.191"}],"container-title":["Molecular Genetics &amp; 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