{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:06:25Z","timestamp":1789607185297,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,6,26]],"date-time":"2017-06-26T00:00:00Z","timestamp":1498435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TR 1018\/3\u20101"],"award-info":[{"award-number":["TR 1018\/3\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003390","name":"Fritz Thyssen Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003390","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>Pathogenic variants in the mitochondrial aminoacyl tRNA synthetases lead to deficiencies in mitochondrial protein synthesis and are associated with a broad range of clinical presentations usually with early onset and inherited in an autosomal recessive manner. Of the 19 mitochondrial aminoacyl tRNA synthetases, <jats:italic>WARS2<\/jats:italic>, encoding mitochondrial tryptophanyl tRNA synthetase, was as of late the only one that had not been associated with disease in humans. A case of a family with pathogenic variants in <jats:italic>WARS2<\/jats:italic> that caused mainly intellectual disability, speech impairment, aggressiveness, and athetosis was recently reported. Here we substantially extend and consolidate the symptomatology of <jats:italic>WARS2<\/jats:italic> by presenting a patient with severe infantile\u2010onset leukoencephalopathy, profound intellectual disability, spastic quadriplegia, epilepsy, microcephaly, short stature, failure to thrive, cerebral atrophy, and periventricular white matter abnormalities. He was found by whole\u2010exome sequencing to have compound heterozygous variants in <jats:italic>WARS2<\/jats:italic>, c.938A&gt;T (p.K313M) and c.298_300delCTT (p.L100del). De novo synthesis of proteins inside mitochondria was reduced in the patient's fibroblasts, leading to significantly lower steady\u2010state levels of respiratory chain subunits compared to control and resulting in lower oxygen consumption rates.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38339","type":"journal-article","created":{"date-parts":[[2017,6,26]],"date-time":"2017-06-26T15:04:39Z","timestamp":1498489479000},"page":"2505-2510","source":"Crossref","is-referenced-by-count":44,"title":["Deficiency of <i>WARS2<\/i>, encoding mitochondrial tryptophanyl tRNA synthetase, causes severe infantile onset leukoencephalopathy"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0785-408X","authenticated-orcid":false,"given":"Benjamin E.","family":"Theisen","sequence":"first","affiliation":[{"name":"Hugo W. Moser Research Institute at Kennedy Krieger Kennedy Krieger Institute Baltimore Maryland"},{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Rumyantseva","sequence":"additional","affiliation":[{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging\u2010Associated Diseases (CECAD) Center for Molecular Medicine and Institute for Mitochondrial Diseases and Aging Medical Faculty University of Cologne Cologne North\u2010Rhine Westfalia Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie S.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Hugo W. Moser Research Institute at Kennedy Krieger Kennedy Krieger Institute Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy A.","family":"Alcaraz","sequence":"additional","affiliation":[{"name":"AmbryGenetics Aliso Viejo California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepali N.","family":"Shinde","sequence":"additional","affiliation":[{"name":"AmbryGenetics Aliso Viejo California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Tang","sequence":"additional","affiliation":[{"name":"AmbryGenetics Aliso Viejo California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddarth","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Department of Pediatrics Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Pevsner","sequence":"additional","affiliation":[{"name":"Hugo W. Moser Research Institute at Kennedy Krieger Kennedy Krieger Institute Baltimore Maryland"},{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Trifunovic","sequence":"additional","affiliation":[{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging\u2010Associated Diseases (CECAD) Center for Molecular Medicine and Institute for Mitochondrial Diseases and Aging Medical Faculty University of Cologne Cologne North\u2010Rhine Westfalia Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Fatemi","sequence":"additional","affiliation":[{"name":"Hugo W. 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