{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T20:24:37Z","timestamp":1785183877378,"version":"3.55.0"},"reference-count":13,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Biallelic pathogenic variants in the <jats:italic>TARS2<\/jats:italic> gene cause combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early\u2010onset severe axial hypotonia, limb hypertonia, delayed psychomotor development, epilepsy, and brain anomalies. Currently, eight COXPD21 patients have been reported in the literature, and 11 pathogenic variants in <jats:italic>TARS2<\/jats:italic> have been identified. Here, we report a 2\u2010year\u20106\u2010month\u2010old Chinese female who presented with severe dystonia, developmental regression, absent speech, and intractable epilepsy. Laboratory examination showed persistently increased serum lactate. Brain MRI showed that the head of the caudate and partial lenticular nucleus were bilateral symmetrical T2\u2010weighted imaging (T2WI) hyperintense and the corpus callosum was very thin. The clinical characteristics pointed to a ME. Trio\u2010based whole\u2010exome sequencing (WES) was employed to detect the causative variants. WES revealed novel compound heterozygous variants, c.470G&gt;C (p.Thr157Arg) and c.2051C&gt;T (p.Arg684Gln), in <jats:italic>TARS2<\/jats:italic> in our patient that were inherited from the mother and father, respectively. Next, we systematically reviewed the available clinical features of COXPD21 patients and noticed that the reduced fetal movement observed in our patient may be a novel phenotype of COXPD21. These findings expand the mutation spectrum of <jats:italic>TARS2<\/jats:italic> and provide insights into the genotype\u2013phenotype relationship in COXPD21 as well as a foundation for its genetic counseling, diagnosis and treatment.<\/jats:p>","DOI":"10.1002\/ajmg.a.62988","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T09:29:56Z","timestamp":1665480596000},"page":"70-76","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Novel <scp><i>TARS2<\/i><\/scp> variant identified in a Chinese patient with mitochondrial encephalomyopathy and a systematic review"],"prefix":"10.1002","volume":"191","author":[{"given":"Peiqing","family":"He","sequence":"first","affiliation":[{"name":"Affiliated Dongguan Maternal and Child Health Care Hospital, Southern Medical University  Dongguan China"},{"name":"Dongguan Institute of Reproductive and Genetic Research  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingming","family":"Wang","sequence":"additional","affiliation":[{"name":"Affiliated Dongguan Maternal and Child Health Care Hospital, Southern Medical University  Dongguan China"},{"name":"Dongguan Institute of Reproductive and Genetic Research  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Hong","sequence":"additional","affiliation":[{"name":"Affiliated Dongguan Maternal and Child Health Care Hospital, Southern Medical University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8510-0419","authenticated-orcid":false,"given":"Haiming","family":"Yuan","sequence":"additional","affiliation":[{"name":"Affiliated Dongguan Maternal and Child Health Care Hospital, Southern Medical University  Dongguan China"},{"name":"Dongguan Institute of Reproductive and Genetic Research  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20170103"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22590"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.11.036"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.01.010"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-020-01149-0"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23277"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12387"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2016.11.013"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2017.06.002"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.700849"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.REV118.002955"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab257"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62988","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62988","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62988","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T09:59:35Z","timestamp":1692439175000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62988"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,11]]},"references-count":13,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1002\/ajmg.a.62988"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62988","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,11]]},"assertion":[{"value":"2022-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}