{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T13:59:51Z","timestamp":1747144791198,"version":"3.40.5"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,8]],"date-time":"2019-05-08T00:00:00Z","timestamp":1557273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571086","81870889","81200965","81430022"],"award-info":[{"award-number":["81571086","81870889","81200965","81430022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","award":["20161401"],"award-info":[{"award-number":["20161401"]}],"id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">GDP<\/jats:styled-content>\u2010mannose pyrophosphorylase B (<jats:styled-content style=\"fixed-case\">GMPPB<\/jats:styled-content>) related phenotype spectrum ranges widely from congenital myasthenic syndrome (<jats:styled-content style=\"fixed-case\">CMS<\/jats:styled-content>), limb\u2010girdle muscular dystrophy type 2T (<jats:styled-content style=\"fixed-case\">LGMD<\/jats:styled-content> 2T) to severe congenital muscle\u2010eye\u2010brain syndrome. Our study investigates the clinicopathologic features of a patient with novel <jats:italic><jats:styled-content style=\"fixed-case\">GMPPB<\/jats:styled-content><\/jats:italic> mutations and explores the pathogenetic mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The patient was a 22\u2010year\u2010old woman with chronic proximal limb weakness for 9\u00a0years without cognitive deterioration. Weakness became worse after fatigue. Elevated serum creatine kinase and decrements on repetitive nerve stimulation test were recorded. <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> showed fatty infiltration in muscles of lower limbs and shoulder girdle on T1 sequence. Open muscle biopsy and genetic analysis were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Muscle biopsy showed myogenic changes. Two missense mutations in <jats:italic><jats:styled-content style=\"fixed-case\">GMPPB<\/jats:styled-content><\/jats:italic> gene (c.803T&gt;C and c.1060G&gt;A) were identified in the patient. Western blotting and immunostaining showed <jats:styled-content style=\"fixed-case\">GMPPB<\/jats:styled-content> and <jats:italic>\u03b1<\/jats:italic>\u2010dystroglycan deficiency in the patient's muscle. In vitro, mutant <jats:styled-content style=\"fixed-case\">GMPPB<\/jats:styled-content> forming cytoplasmic aggregates completely colocalized with microtubule\u2010associated protein 1 light chain 3\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>), a classical marker of autophagosome. Degradation of <jats:styled-content style=\"fixed-case\">GMPPB<\/jats:styled-content> was accompanied by an upregulation of <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>, which could be restored by lysosomal inhibitor leupeptin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We identified two novel <jats:italic><jats:styled-content style=\"fixed-case\">GMPPB<\/jats:styled-content><\/jats:italic> mutations causing overlap phenotype between <jats:styled-content style=\"fixed-case\">LGMD<\/jats:styled-content> 2T and <jats:styled-content style=\"fixed-case\">CMS<\/jats:styled-content>. We provided the initial evidence that mutant <jats:styled-content style=\"fixed-case\">GMPPB<\/jats:styled-content> colocalizes with autophagosome at subcellular level. <jats:styled-content style=\"fixed-case\">GMPPB<\/jats:styled-content> mutants degraded by autophagy\u2010lysosome pathway is associated with <jats:styled-content style=\"fixed-case\">LGMD<\/jats:styled-content> 2T. This study shed the light into the enzyme replacement which could become one of the therapeutic targets in the future study.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.787","type":"journal-article","created":{"date-parts":[[2019,5,8]],"date-time":"2019-05-08T07:37:08Z","timestamp":1557301028000},"page":"1062-1071","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Lysosomal degradation of <scp>GMPPB<\/scp> is associated with limb\u2010girdle muscular dystrophy type 2T"],"prefix":"10.1002","volume":"6","author":[{"given":"Wo\u2010Tu","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Neurology Rui Jin Hospital &amp; Rui Jin Hospital North Shanghai Jiao Tong University School of Medicine Shanghai 200025 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai\u2010Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology Rui Jin Hospital &amp; Rui Jin Hospital North Shanghai Jiao Tong University School of Medicine Shanghai 200025 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei\u2010Xia","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Neurology Rui Jin Hospital &amp; Rui Jin Hospital North Shanghai Jiao Tong University School of Medicine Shanghai 200025 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ze\u2010Yu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology Rui Jin Hospital &amp; Rui Jin Hospital North Shanghai Jiao Tong University School of Medicine Shanghai 200025 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Core Facility of Basic Medical Sciences Shanghai Jiao Tong University School of Medicine Shanghai 200025 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng\u2010Di","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Rui Jin Hospital &amp; Rui Jin Hospital North Shanghai Jiao Tong University School of Medicine Shanghai 200025 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing\u2010Hua","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Neurology Rui Jin Hospital &amp; Rui Jin Hospital North Shanghai Jiao Tong University School of Medicine Shanghai 200025 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1742-9877","authenticated-orcid":false,"given":"Li","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurology Rui Jin Hospital &amp; Rui Jin Hospital North Shanghai Jiao Tong University School of Medicine Shanghai 200025 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.009"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv185"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv013"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22898"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2000.01781.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02814"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/355696a0"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01195-9"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2018.05.007"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.03.004"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316956"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000324927.28817.9b"},{"key":"e_1_2_10_15_1","first-page":"95","article-title":"Muscle MRI in muscular dystrophies","volume":"34","author":"D\u00edaz\u2010Manera J","year":"2015","journal-title":"Acta Myol"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1100356"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0863-x"},{"key":"e_1_2_10_18_1","first-page":"1","article-title":"Genetic basis of limb\u2010girdle muscular dystrophies: the 2014 update","volume":"33","author":"Nigro V","year":"2014","journal-title":"Acta Myol"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.04.028"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000112"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(83)90131-9"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200501724"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2018.00128"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(02)00390-4"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2004.09.025"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2245"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facn3.787","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.787","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.787","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.787","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T19:18:57Z","timestamp":1694373537000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,8]]},"references-count":25,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1002\/acn3.787"],"URL":"https:\/\/doi.org\/10.1002\/acn3.787","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"type":"print","value":"2328-9503"},{"type":"electronic","value":"2328-9503"}],"subject":[],"published":{"date-parts":[[2019,5,8]]},"assertion":[{"value":"2019-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}