{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T20:48:52Z","timestamp":1778705332074,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":246,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Global developmental delay (GDD) and intellectual disability (ID) affect up to 3% of the paediatric population, with a multifactorial aetiology that complicates genetic identification. To date, over 400 genes have been implicated in GDD. Here, we report a novel homozygous splice acceptor variant, NC_000001.11(NM_017646.6):c.1235\u20103C&gt;G, in the\n                    <jats:italic>TRIT1<\/jats:italic>\n                    gene, classified as \u2018likely pathogenic\u2019 through bioinformatics analysis. The proband, a 5\u2010year\u2010old male from a consanguineous family, presented with severe GDD, microcephaly, progressive spasticity, contractures, dysmorphic features (low\u2010set ears, high\u2010arched palate, simian creases and hypospadias), and refractory seizures (focal motor clonic, generalized myoclonic, and tonic) since 6\u2009months of age. Brain MRI revealed nonspecific atrophy, while metabolic, laboratory and electrophysiological evaluations were unremarkable. To further assess the variant's frequency, we screened 430 healthy individuals from the same ethnic group and found no occurrences of the variant. Notably, this variant has not been documented in any published population databases, including gnomAD, the 1000 Genomes Project, Genome Asia, GME Variome and Iranome, despite coverage of the locus in these databases. Taken together, these findings strongly support the potential pathogenicity of the variant. In addition, the prenatal diagnosis results from the subsequent pregnancy in this family showed that the embryo was heterozygous for the mutation. The baby was born, and follow\u2010up studies indicated that she was healthy, with no clinical manifestations observed in her affected brother. This further supports the classification of the variant as \u2018likely pathogenic.\u2019 This study expands the phenotypic spectrum of\n                    <jats:italic>TRIT1<\/jats:italic>\n                    \u2010related disorders.\n                  <\/jats:p>","DOI":"10.1002\/jdn.70053","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T04:31:10Z","timestamp":1757046670000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of a Novel TRIT1 Mutation in a Consanguineous Iranian\u2013Azeri\u2013Turkish Family With Global Developmental Delay"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4755-7905","authenticated-orcid":false,"given":"Fatemeh","family":"Beyad","sequence":"first","affiliation":[{"name":"Animal Biology Department, Faculty of Natural Sciences University of Tabriz  Tabriz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3216-2947","authenticated-orcid":false,"given":"Mortaza","family":"Bonyadi","sequence":"additional","affiliation":[{"name":"Center of Excellence for Biodiversity, Faculty of Natural Sciences University of Tabriz  Tabriz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5503-9039","authenticated-orcid":false,"given":"Mohammad","family":"Barzegar","sequence":"additional","affiliation":[{"name":"Pediatric Health Research Center, Mardani Azari Children Hospital Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"1000 Genome Project. n.d. \u201cA Deep Catalog of Human Genetic Variation.\u201d Accessed May 5 2024 https:\/\/www.internationalgenome.org."},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.2129"},{"key":"e_1_2_13_4_1","unstructured":"Clinvar National Library of Medicine. n.d. Accessed May 5 2024.https:\/\/www.ncbi.nlm.nih.gove\/clinvar."},{"key":"e_1_2_13_5_1","unstructured":"dbSNP NCBI SNP database. n.d. Accessed May 26 2024.https:\/\/www.ncbi.nlm.nih.gov\/snp."},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10295"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2020.103882"},{"key":"e_1_2_13_8_1","unstructured":"GenomAD The Genome Aggregation Database. n.d. Accessed May 5 2024.https:\/\/gnomad.broadinstitute.org."},{"key":"e_1_2_13_9_1","unstructured":"Iranome. n.d. \u201cWorld Wide Web.\u201d Accessed May 05 2024.https:\/\/iranome.com."},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23196"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.170216"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21062"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.15386\/cjmed\u2010461"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-1839"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12550"},{"key":"e_1_2_13_18_1","unstructured":"OMIM Online Mendelian Inheritance in Man.OMIM. Johns Hopkins University Baltimore MD. MIM Number: 610467: 01\/08\/2016.2016 accessed May 26 2024.https:\/\/omim.org\/."},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.5.1185"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.1997.4.311"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt291"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104603"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.115"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61211"},{"key":"e_1_2_13_26_1","article-title":"The UniProt Consortium; The Universal Protein Knowledgebase in 2023","volume":"51","author":"UniProt","year":"2023","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0477-0"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.105"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004424"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1159\/000518373"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2020.08.016"}],"container-title":["International Journal of Developmental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jdn.70053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T07:55:58Z","timestamp":1763020558000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jdn.70053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/jdn.70053"],"URL":"https:\/\/doi.org\/10.1002\/jdn.70053","archive":["Portico"],"relation":{},"ISSN":["0736-5748","1873-474X"],"issn-type":[{"value":"0736-5748","type":"print"},{"value":"1873-474X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2025-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70053"}}