{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T16:21:10Z","timestamp":1771258870403,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T00:00:00Z","timestamp":1552348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2019.00259","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T05:40:35Z","timestamp":1552369235000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Compound Heterozygous CHAT Gene Mutations of a Large Deletion and a Missense Variant in a Chinese Patient With Severe Congenital Myasthenic Syndrome With Episodic Apnea"],"prefix":"10.3389","volume":"10","author":[{"given":"Zhimei","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danmin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changhong","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiuwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suyun","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2019,3,12]]},"reference":[{"key":"B1","article-title":"Congenital myasthenic syndromes","author":"Abicht","year":"","journal-title":"Source<sup>\u00ae<\/sup> registered GeneReviews"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7.20.1","DOI":"10.1002\/0471142905.hg0270s76","article-title":"Predicting functional effect of human missense mutations using PolyPhen-2.","volume":"76","author":"Adzhubei","year":"2013","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.ejpn.2011.03.006","article-title":"Genetic heterogeneity and pathophysiological mechanisms in congenital myasthenic syndromes.","volume":"15","author":"Barisic","year":"2011","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/S0022-3476(75)80651-2","article-title":"Familial infantile myasthenia gravis: a cause of sudden death in young children.","volume":"87","author":"Conomy","year":"1975","journal-title":"J. Pediatr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1177\/0883073812470000","article-title":"Congenital myasthenic syndrome due to choline acetyltransferase mutations in infants: clinical suspicion and comprehensive electrophysiological assessment are important for early diagnosis.","volume":"29","author":"Dilena","year":"2014","journal-title":"J. Child Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/B978-0-444-64076-5.00037-5","article-title":"Genetic basis and phenotypic features of congenital myasthenic syndromes.","volume":"148","author":"Engel","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/ana.410010403","article-title":"A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small nerve terminals, and reduced acetylcholine release.","volume":"1","author":"Engel","year":"1977","journal-title":"Ann. Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/S1474-4422(14)70201-7","article-title":"Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment.","volume":"14","author":"Engel","year":"2015","journal-title":"Lancet Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1007\/s11427-017-9080-y","article-title":"The clinical and genetic characteristics in children with mitochondrial disease in China.","volume":"60","author":"Fang","year":"2017","journal-title":"Sci. China Life Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1038\/ng.3703","article-title":"M-CAP eliminates a majority of variants of uncertain significance in clinical exomes at high sensitivity.","volume":"48","author":"Jagadeesh","year":"2016","journal-title":"Nat. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"D937","DOI":"10.1093\/nar\/gkx1062","article-title":"eRAM: encyclopedia of rare disease annotations for precision medicine.","volume":"46","author":"Jia","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1007\/s11427-017-9099-3","article-title":"Towards efficiency in rare disease research: what is distinctive and important?","volume":"60","author":"Jia","year":"2017","journal-title":"Sci. China Life Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1002\/ped4.12044","article-title":"Application of genome analysis strategies in the clinical testing for pediatric diseases.","volume":"2","author":"Jin","year":"2018","journal-title":"Pediatr. Investig."},{"key":"B14","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1101\/gr.129684.111","article-title":"VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing.","volume":"22","author":"Koboldt","year":"2012","journal-title":"Genome Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans.","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and accurate long-read alignment with Burrows-Wheeler transform.","volume":"26","author":"Li","year":"2010","journal-title":"Bioinformatics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and SAMtools.","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.pediatrneurol.2009.02.017","article-title":"Congenital myasthenic syndrome with episodic apnea.","volume":"41","author":"Mallory","year":"2009","journal-title":"Pediatr. Neurol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: predicting amino acid changes that affect protein function.","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/s11427-017-9100-1","article-title":"The challenge and promise of rare disease diagnosis in China.","volume":"60","author":"Ni","year":"2017","journal-title":"Sci. China Life Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1046\/j.1440-1827.1999.00977.x","article-title":"Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system.","volume":"49","author":"Oda","year":"1999","journal-title":"Pathol. Int."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1073\/pnas.98.4.2017","article-title":"Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans.","volume":"98","author":"Ohno","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B23","doi-asserted-by":"publisher","first-page":"D490","DOI":"10.1093\/nar\/gky1130","article-title":"The SUPERFAMILY 2.0 database: a significant proteome update and a new webserver.","volume":"47","author":"Pandurangan","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19061677","article-title":"The neuromuscular junction and wide heterogeneity of congenital myasthenic syndromes.","volume":"19","author":"Rodriguez","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.ejpn.2009.09.009","article-title":"Long-term follow-up in patients with congenital myasthenic syndrome due to CHAT mutations.","volume":"14","author":"Schara","year":"2010","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/nmeth0810-575","article-title":"MutationTaster evaluates disease-causing potential of sequence alterations.","volume":"7","author":"Schwarz","year":"2010","journal-title":"Nat. Methods"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data.","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1002\/ped4.12045","article-title":"Next-generation sequencing applied in pediatric diseases.","volume":"2","author":"Yu","year":"2018","journal-title":"Pediatr. Investig."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.00259\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T05:40:37Z","timestamp":1552369237000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.00259\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,12]]},"references-count":28,"alternative-id":["10.3389\/fphar.2019.00259"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2019.00259","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,12]]},"article-number":"259"}}