{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:31:09Z","timestamp":1789655469932,"version":"4.0.1"},"reference-count":8,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Isoleucinyl\u2010tRNA synthetase (IARS) is encoded by the\n IARS1<\/jats:italic>\n gene and catalyzes the binding of isoleucine to specific tRNA.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n This study aims to investigate the pathogenicity of novel\n IARS1<\/jats:italic>\n variants and the genotype\u2013phenotype association, in order to expand the spectrum of pathogenic variants and phenotypes of\n IARS1<\/jats:italic>\n \u2010related disease and provide new evidence for the phenotypic spectrum of\n IARS1<\/jats:italic>\n variants.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Clinical data of the proband were collected, and trio whole\u2010exome sequencing (WES) was performed on the proband and the parents. Candidate variants were validated using Sanger sequencing. Bioinformatics software was utilized to analyze the functional consequences of identified variants and predict their potential deleteriousness.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A 17\u2010month\u2010old female patient presented with microcephaly, left external ear malformation, decreased muscle strength and tone in all limbs, epileptic seizures, global developmental delay, and developmental regression. Trio WES identified compound heterozygous variants in the\n IARS1<\/jats:italic>\n gene, c.120\u20101G>A and c.2164C>A, which were novel pathogenic and likely pathogenic variants, respectively. The phenotype of developmental regression has not been reported before. Only one patient with\n IARS1<\/jats:italic>\n compound heterozygous variants has been reported in the world to have an epileptic phenotype, and this is the second patient with an epileptic phenotype. Bioinformatics analysis revealed that the splicing variant disrupted the canonical splice donor site, while the missense variant altered the local electrostatics of the\n IARS1<\/jats:italic>\n protein surface, potentially leading to functional abnormalities.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This study identified novel\n IARS1<\/jats:italic>\n variants and the phenotype of developmental regression, expanding the spectrum of pathogenic variants and phenotypes of\n IARS1<\/jats:italic>\n \u2010related diseases and providing new evidence for the rare phenotype of epileptic seizures caused by\n IARS1<\/jats:italic>\n variants.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.2326","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T04:05:58Z","timestamp":1701144358000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel\n IARS1<\/i>\n variants cause syndromic developmental disorder with epilepsy in a Chinese patient and the literature review"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0846-0242","authenticated-orcid":false,"given":"Jinsong","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Paediatric Medicine Shanxi Medical University Taiyuan Shanxi People's Republic of China"},{"name":"Department of Cytogenetic Laboratory, Children's Hospital of Shanxi Women Health Center of Shanxi, Affiliated Hospital of Shanxi Medical University Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Paediatric Medicine Shanxi Medical University Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyin","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Paediatric Medicine Shanxi Medical University Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Paediatric Medicine Shanxi Medical University Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Paediatric Medicine Shanxi Medical University Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianrui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cytogenetic Laboratory, Children's Hospital of Shanxi Women Health Center of Shanxi, Affiliated Hospital of Shanxi Medical University Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cytogenetic Laboratory, Children's Hospital of Shanxi Women Health Center of Shanxi, Affiliated Hospital of Shanxi Medical University Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cytogenetic Laboratory, Children's Hospital of Shanxi Women Health Center of Shanxi, Affiliated Hospital of Shanxi Medical University Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiayu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cytogenetic Laboratory, Children's Hospital of Shanxi Women Health Center of Shanxi, Affiliated Hospital of Shanxi Medical University Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbo","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cytogenetic Laboratory, Children's Hospital of Shanxi Women Health Center of Shanxi, Affiliated Hospital of Shanxi Medical University Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqin","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Cytogenetic Laboratory, Children's Hospital of Shanxi Women Health Center of Shanxi, Affiliated Hospital of Shanxi Medical University Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24430"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0048-y"},{"issue":"1","key":"e_1_2_10_4_1","first-page":"94","article-title":"A case of GRIDHH due to mutations in the IARS gene","volume":"29","author":"Guojie W. B. R.","year":"2021","journal-title":"Chinese Journal of Birth Health & Heredity"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.05.027"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12930"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13080"}],"container-title":["Molecular Genetics & Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2326","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T07:25:08Z","timestamp":1706513108000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,28]]},"references-count":8,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/mgg3.2326"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2326","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,28]]},"assertion":[{"value":"2023-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2326"}}