{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:47:48Z","timestamp":1791978468720,"version":"4.4.0"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["NU22\u201007\u201000165"],"award-info":[{"award-number":["NU22\u201007\u201000165"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital myasthenic syndromes (CMSs) are characterized by hypotonia, episodic apnea, muscle weakness, ptosis and generalized fatigability. CMS type 20 (CMS20) is a rare disorder caused by variants in <jats:italic>SLC5A7<\/jats:italic>. In contrast to most other CMSs, CMS20 is also associated with neurodevelopmental disorders (NDDs). Only 19 patients from 14 families have been reported so far.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied a 12\u2010year\u2010old boy with symptoms manifested at six weeks of age. Later, he also showed speech delay, moderate intellectual disability and autism. Analysis of CMS genes known at the time of clinical diagnosis yielded no results. Trio exome sequencing (ES) was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ES revealed compound heterozygosity for two <jats:italic>SLC5A7<\/jats:italic> variants, p.(Asn431Lys) and p.(Ile291Thr). While the first variant was absent from all databases, the second variant has already been described in one patient. In silico analysis of known pathogenic <jats:italic>SLC5A7<\/jats:italic> variants showed that variants with a higher predicted deleteriousness may be associated with earlier onset and increased severity of neuromuscular manifestations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our patient confirms that CMS20 can be associated with NDDs. The study illustrates the strength of ES in deciphering the genetic basis of rare diseases, contributes to characterization of CMS20 and suggests trends in genotype\u2013phenotype correlation in CMS20.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2154","type":"journal-article","created":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T06:40:15Z","timestamp":1677307215000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A new patient with congenital myasthenic syndrome type 20 due to compound heterozygous missense <i>SLC5A7<\/i> variants suggests trends in genotype\u2013phenotype correlation"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1496-392X","authenticated-orcid":false,"given":"Marketa","family":"Vlckova","sequence":"first","affiliation":[{"name":"Department of Biology and Medical Genetics Charles University Second Faculty of Medicine and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3266-6523","authenticated-orcid":false,"given":"Darina","family":"Prchalova","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics Charles University Second Faculty of Medicine and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3455-4899","authenticated-orcid":false,"given":"Pavel","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Statistics and Probability, Faculty of Informatics and Statistics University of Economics  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2734-9715","authenticated-orcid":false,"given":"Jana","family":"Haberlova","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Charles University Second Faculty of Medicine and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-7995","authenticated-orcid":false,"given":"Sarka","family":"Bendova","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics Charles University Second Faculty of Medicine and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Moslerova","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics Charles University Second Faculty of Medicine and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2599-6479","authenticated-orcid":false,"given":"Viktor","family":"Stranecky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Diagnostic and Research Unit for Rare Diseases Charles University First Faculty of Medicine and General University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6575-9163","authenticated-orcid":false,"given":"Zdenek","family":"Sedlacek","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics Charles University Second Faculty of Medicine and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-8862","authenticated-orcid":false,"given":"Miroslava","family":"Hancarova","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics Charles University Second Faculty of Medicine and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23828"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.09.019"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.033"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8689-3"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/72059"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2018.06.020"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2020.10.006"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19061677"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/ETLS20180100"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx249"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.2154","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T16:09:39Z","timestamp":1692547779000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,24]]},"references-count":10,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/mgg3.2154"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2154","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,24]]},"assertion":[{"value":"2022-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2154"}}