{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T20:24:39Z","timestamp":1785183879180,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"21-22","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012155","name":"National Institute for Medical Research Development","doi-asserted-by":"publisher","award":["electronic application No: 983886"],"award-info":[{"award-number":["electronic application No: 983886"]}],"id":[{"id":"10.13039\/501100012155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>NARS2<\/jats:italic> encodes mitochondrial Asparaginyl\u2010tRNA Synthetase 2, which catalyzes the aminoacylation of tRNA\u2010Asn in the mitochondria. To date, 24 variants have been reported in <jats:italic>NARS2<\/jats:italic> gene in 35 patients. The phenotypic variability of <jats:italic>NARS2\u2010<\/jats:italic>associated disorder is broad, ranging from neurodevelopmental disorders to hearing loss. In this study, we report some novel imaging findings in an Iranian patient suffering from epileptic encephalopathy, caused by a previously reported variant, c.500A\u2009&gt;\u2009G; p.(His167Arg), in <jats:italic>NARS2<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The spectrum of clinical manifestations of two Iranian patients was investigated and genetic analysis was performed by Whole\u2010exome sequencing (WES). Additionally, we also reviewed the literature and summarized the phenotypes of previously reported patients with variants in the <jats:italic>NARS2<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we present the phenotypic and genetic features of 2 unrelated Iranian infants presented with neurodevelopmental delay, seizures, hearing impairment, feeding problems, elevated serum lactate levels in addition to subdural hematoma and cerebral parenchymal hemorrhage in the brain magnetic resonance imaging (MRI) of one of the patients. Genetic analysis revealed a biallelic missense variant in <jats:italic>NARS2<\/jats:italic>: c.500A\u2009&gt;\u2009G; p.(His167Arg). We described the subdural hematoma and cerebral parenchymal hemorrhage of the brain for the first time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study provides new clinical findings, subdural hematoma, and parenchymal hemorrhage, in <jats:italic>NARS2<\/jats:italic>\u2010related disorders. Our findings along with previous studies provide more evidence of the clinical presentation of the disease caused by pathogenic variants in <jats:italic>NARS2<\/jats:italic>. Expanding the clinical spectrum increases the diagnostic rate of molecular testing and improves the quality of counseling for at\u2010risk couples.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24983","type":"journal-article","created":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T07:33:46Z","timestamp":1699688026000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expanding phenotype heterogeneity of <i>NARS2<\/i> by presenting subdural hematoma and parenchymal hemorrhage"],"prefix":"10.1002","volume":"37","author":[{"given":"Mehrnoosh","family":"Khodaeian","sequence":"first","affiliation":[{"name":"Department of Medical Genetics DeNA Laboratory  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4489-2923","authenticated-orcid":false,"given":"Fatemeh","family":"Bitarafan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Oslo University Hospital and University of Oslo  0450 Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Garrousi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics DeNA Laboratory  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham Amjadi","family":"Sardehie","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics DeNA Laboratory  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Pak","sequence":"additional","affiliation":[{"name":"Pediatric Radiology Division, Children's Medical Center, Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sareh","family":"Hosseinpour","sequence":"additional","affiliation":[{"name":"Myelin Disorders Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of 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