{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:44:57Z","timestamp":1778852697268,"version":"3.51.4"},"reference-count":10,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004061","name":"Oesterreichische Nationalbank (OeNB)","doi-asserted-by":"publisher","award":["18023"],"award-info":[{"award-number":["18023"]}],"id":[{"id":"10.13039\/501100004061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004061","name":"Oesterreichische Nationalbank (OeNB)","doi-asserted-by":"publisher","award":["01GM1920A"],"award-info":[{"award-number":["01GM1920A"]}],"id":[{"id":"10.13039\/501100004061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004061","name":"Oesterreichische Nationalbank (OeNB)","doi-asserted-by":"publisher","award":["I4695-B"],"award-info":[{"award-number":["I4695-B"]}],"id":[{"id":"10.13039\/501100004061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian science fund (FWF)","doi-asserted-by":"publisher","award":["18023"],"award-info":[{"award-number":["18023"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian science fund (FWF)","doi-asserted-by":"publisher","award":["01GM1920A"],"award-info":[{"award-number":["01GM1920A"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian science fund (FWF)","doi-asserted-by":"publisher","award":["I4695-B"],"award-info":[{"award-number":["I4695-B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Heterozygous deletions at 19q12\u2013q13.11 affecting TSHZ3, the teashirt zinc finger homeobox 3, have been associated with intellectual disability and behavioural issues, congenital anomalies of the kidney and urinary tract (CAKUT), and postnatal growth retardation in humans and mice. TSHZ3 encodes a transcription factor regulating the development of neurons but is ubiquitously expressed. Using exome sequencing, we identified a heterozygous frameshift variant c.119_120dup p.Pro41SerfsTer79 in TSHZ3 in a 7-year-old girl with intellectual disability, behavioural issues, pyelocaliceal dilatation, and mild urethral stenosis. The variant was present on the paternal TSHZ3 allele. The DNA from the father was not available for testing. This is the first report of a heterozygous point mutation in TSHZ3 causing the same phenotype as reported for monoallelic deletions in the same region. This confirms TSHZ3 as a novel disease gene for neurodevelopmental disorder in combination with behavioural issues and CAKUT.<\/jats:p>","DOI":"10.3390\/genes13122191","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T01:46:56Z","timestamp":1669254416000},"page":"2191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A TSHZ3 Frame-Shift Variant Causes Neurodevelopmental and Renal Disorder Consistent with Previously Described Proximal Chromosome 19q13.11 Deletion Syndrome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-8258","authenticated-orcid":false,"given":"Ren\u00e9 G.","family":"Feichtinger","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Preisel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Steinbr\u00fccker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6440-1036","authenticated-orcid":false,"given":"Karin","family":"Brugger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Radda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital Villach, 9500 Villach, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1968-8103","authenticated-orcid":false,"given":"Saskia B.","family":"Wortmann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria"},{"name":"Amalia Children\u2019s Hospital, Radboudumc, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6970-336X","authenticated-orcid":false,"given":"Johannes A.","family":"Mayr","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/ng.3681","article-title":"TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons","volume":"48","author":"Caubit","year":"2016","journal-title":"Nat. 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Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/ajmg.a.36201","article-title":"Phenotypic and molecular characterization of 19q12q13.1 deletions: A report of five patients","volume":"164","author":"Chowdhury","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1136\/jmg.2008.062034","article-title":"19q13.11 deletion syndrome: A novel clinically recognisable genetic condition identified by array comparative genomic hybridisation","volume":"46","author":"Malan","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s10519-019-09970-x","article-title":"Construct Validity and Cross Validity of a Test Battery Modeling Autism Spectrum Disorder (ASD) in Mice","volume":"50","author":"Roubertoux","year":"2020","journal-title":"Behav. 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Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/ki.2015.319","article-title":"Prioritization and burden analysis of rare variants in 208 candidate genes suggest they do not play a major role in CAKUT","volume":"89","author":"Nicolaou","year":"2016","journal-title":"Kidney Int."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/12\/2191\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:25:04Z","timestamp":1760145904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/12\/2191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,23]]},"references-count":10,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["genes13122191"],"URL":"https:\/\/doi.org\/10.3390\/genes13122191","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,23]]}}}