{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:42:46Z","timestamp":1778751766919,"version":"3.51.4"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"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":["Muscle and Nerve"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Biallelic mutations in <jats:italic>TBC1\u2010domain containing kinase<\/jats:italic> (<jats:italic>TBCK<\/jats:italic>) lead to hypotonia, global developmental delay with severe cognitive and motor deficits, and variable presentation of dysmorphic facial features and brain malformations. It remains unclear whether hypotonia in these individuals is purely neurogenic, or also caused by progressive muscle disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole exome sequencing was performed on a family diagnosed with nonspecific myopathic changes by means of histological analysis and immunohistochemistry of muscle biopsy samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel homozygous truncation in <jats:italic>TBCK<\/jats:italic> was found in two sisters diagnosed with muscle disease and severe psychomotor delay. TBCK was completely absent in these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings identify a novel early truncating variant in <jats:italic>TBCK<\/jats:italic> associated with a severe presentation and add muscle disease to the variability of phenotypes associated with <jats:italic>TBCK<\/jats:italic> mutations. Inconsistent genotype\/phenotype correlation could be ascribed to the multiple roles of TBCK in intracellular signaling and endolysosomal function in different tissues.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.26907","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T05:15:56Z","timestamp":1588569356000},"page":"266-271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Myopathic changes associated with psychomotor delay and seizures caused by a novel homozygous mutation in <scp><i>TBCK<\/i><\/scp>"],"prefix":"10.1002","volume":"62","author":[{"given":"Simona","family":"Saredi","sequence":"first","affiliation":[{"name":"Neuromuscular Disease and Immunology Unit Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edmund S.","family":"Cauley","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience and Department of Pharmacology and Physiology George Washington University  Washington, DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Ruggieri","sequence":"additional","affiliation":[{"name":"Neuromuscular Disease and Immunology Unit Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta  Milan Italy"},{"name":"Biology and Genetic Division, Molecular and Translational Medicine Department University of Brescia  Brescia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler M.","family":"Spivey","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience and Department of Pharmacology and Physiology George Washington University  Washington, DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Ardissone","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Mora","sequence":"additional","affiliation":[{"name":"Neuromuscular Disease and Immunology Unit Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Moroni","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Chiara","family":"Manzini","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience and Department of Pharmacology and Physiology George Washington University  Washington, DC"},{"name":"Child Health Institute of New Jersey and Department of Neuroscience and Cell Biology Rutgers Robert Wood Johnson Medical School  New Brunswick, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.015"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.03.016"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.01.016"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25130"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.08.004"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38019"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000076"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3592"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2019.02.001"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0646-6"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(96)00298-6"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2013.12.006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071349"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100406200"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21624"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-016-0091-9"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200903131"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.07.027"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmus.26907","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.26907","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.26907","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.26907","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T07:18:59Z","timestamp":1693898339000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.26907"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,27]]},"references-count":23,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1002\/mus.26907"],"URL":"https:\/\/doi.org\/10.1002\/mus.26907","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,27]]},"assertion":[{"value":"2019-10-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}