{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:02:13Z","timestamp":1753869733853,"version":"3.41.2"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"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":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pathogenic variants of <jats:italic>ATP1A2<\/jats:italic> (OMIM ID: 182340) are usually associated with familial hemiplegic migraine type 2 (FHM\u20102), alternating hemiplegia of childhood (AHC), early infantile epileptic encephalopathy (EIEE), transient cytotoxic edema, and so on. Here, we present a novel heterozygous <jats:italic>ATP1A2<\/jats:italic> variant in a girl with alternating hemiplegia, febrile seizures, developmental delay (which subsequently subsided), and MELAS\u2010like syndrome (as indicated by brain MRI). The patient did not experience migraine with aura.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The patient was an 8\u2010year\u2010old girl with normal growth and development. Beginning from the age of 3\u2009years and 8\u2009months, the patient experienced several episodes of alternating limb paralysis. The episodes were accompanied by the appearance of MELAS\u2010like findings on brain MRI, which corresponded to the hemiplegia. There were abnormal linear signals in the cerebral cortex on the opposite side of the hemiplegic limb. Each time the patient recovered from hemiplegia, and each time MRI showed no lesions remained after recovery. No obvious abnormality was found in other examinations. Finally, the patient underwent whole\u2010exome sequencing (WES).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WES revealed a novel and de novo heterozygous variant in the <jats:italic>ATP1A2<\/jats:italic> (NM_000702.3) c.335C&gt;A:p.Ala112Asp (not previously reported). We examined the variant position in the 3D protein structure and found that a missense mutation at this site is a nonconservative substitution. The variation is nonpolymorphic. It occurs at a very low frequency in the population, and its ACMG classification is likely pathogenic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>At present, there are limited reports of mutations in the <jats:italic>ATP1A2<\/jats:italic> gene causing AHC. This is the first case of brain MRI showing MELAS\u2010like imaging in an AHC patient, and more cases are needed for verification. Early genetic testing and family screening can aid in the diagnosis and treatment of genetic diseases. The relationship between <jats:italic>ATP1A2<\/jats:italic> gene mutation genotype and clinical phenotype needs to be further studied.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2146","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T19:10:00Z","timestamp":1675797000000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel heterozygous <scp><i>ATP1A2<\/i><\/scp> pathogenic variant in a Chinese child with <scp>MELAS<\/scp>\u2010like alternating hemiplegia"],"prefix":"10.1002","volume":"11","author":[{"given":"Xin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatrics Linyi People's Hospital, Postgrad Training Base Jinzhou Med University  Linyi People's Republic of China"},{"name":"Department of Pediatrics Linyi People's Hospital  Linyi Shandong People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Linyi People's Hospital  Linyi Shandong People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-3187","authenticated-orcid":false,"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Linyi People's Hospital  Linyi Shandong People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Linyi People's Hospital  Linyi Shandong People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Linyi People's Hospital  Linyi Shandong People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Linyi People's Hospital  Linyi Shandong People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changrui","family":"Mi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Linyi People's Hospital  Linyi Shandong People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menglin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Linyi People's Hospital  Linyi Shandong People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073813504623"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194\u2010021\u201001221\u2010x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.017863"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20103476(06)80003\u2010X"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2021.01.004"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1081"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008212"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2017.05.041"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2020.100609"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37808"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2358"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000117128"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010021\u201000947\u20106"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2013.09.007"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056120"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010103"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2017.12.012"},{"volume-title":"Hemiplegic migraine","year":"2022","author":"Kumar A.","key":"e_1_2_10_19_1"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468\u20102982.2008.01603.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.25736"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2018.07.012"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940\u2010017\u20100444\u20107"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887\u20108994(00)00157\u20100"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2021.05.004"},{"issue":"2","key":"e_1_2_10_26_1","first-page":"133","article-title":"Characteristic asymmetric abnormal eye movement and dystonic posture as the first symptoms of alternating hemiplegia of childhood","volume":"48","author":"Motoki T.","year":"2016","journal-title":"Life Sciences"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.107732"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20102008\u20101027115"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq295"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23149"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2017.02.001"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2017.03.003"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760\u2010017\u20100867\u20107"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(12)70182\u20105"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887\u20108994(98)00016\u20102"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387\u20107604(12)80144\u20106"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2019.10.003"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy283"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100038\u20101677514"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1207\/s15324826an1201_8"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2020.35.e203"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0578\u20101310.2018.11.004"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883\u2010019\u20101306\u20106"},{"key":"e_1_2_10_44_1","first-page":"1","article-title":"The dynamics of the cell membrane coupling of the reaction of the Na, K\u2010ATPase with ATP to the reaction with the cations","volume":"7","author":"Skou J. C.","year":"1982","journal-title":"The Tokai Journal of Experimental Clinical Medicine"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000303"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2014.09.015"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20134"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioaa093"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017\u20100852"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.47.4.675"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2014.06.014"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.06.003"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.24920\/003850"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097274"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13539"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011543"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2146","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.2146","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2146","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T07:47:24Z","timestamp":1692517644000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":55,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1002\/mgg3.2146"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2146","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2023,2,7]]},"assertion":[{"value":"2022-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2146"}}