{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:55:35Z","timestamp":1790420135155,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T00:00:00Z","timestamp":1591142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003768","name":"Universit\u00e9 de Strasbourg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003768","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Glycogen storage diseases (GSDs) are severe human disorders resulting from abnormal glucose metabolism, and all previously described GSDs segregate as autosomal recessive or X\u2010linked traits. In this study, we aimed to molecularly characterize the first family with a dominant GSD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We describe a dominant GSD family with 13 affected members presenting with adult\u2010onset muscle weakness, and we provide clinical, metabolic, histological, and ultrastructural data. We performed exome sequencing to uncover the causative gene, and functional experiments in the cell model and on recombinant proteins to investigate the pathogenic effect of the identified mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a heterozygous missense mutation in <jats:italic>PYGM<\/jats:italic> segregating with the disease in the family. <jats:italic>PYGM<\/jats:italic> codes for myophosphorylase, the enzyme catalyzing the initial step of glycogen breakdown. Enzymatic tests revealed that the <jats:italic>PYGM<\/jats:italic> mutation impairs the AMP\u2010independent myophosphorylase activity, whereas the AMP\u2010dependent activity was preserved. Further functional investigations demonstrated an altered conformation and aggregation of mutant myophosphorylase, and the concurrent accumulation of the intermediate filament desmin in the myofibers of the patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Overall, this study describes the first example of a dominant glycogen storage disease in humans, and elucidates the underlying pathomechanisms by deciphering the sequence of events from the PYGM mutation to the accumulation of glycogen in the muscle fibers. <jats:bold>ANN NEUROL 2020;88:274\u2013282.<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25771","type":"journal-article","created":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T18:50:07Z","timestamp":1589050207000},"page":"274-282","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A New Glycogen Storage Disease Caused by a Dominant <scp><i>PYGM<\/i><\/scp> Mutation"],"prefix":"10.1002","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1012-9783","authenticated-orcid":false,"given":"Andoni","family":"Echaniz\u2010Laguna","sequence":"first","affiliation":[{"name":"Department of Neurology APHP, CHU de Bic\u00eatre  Le Kremlin Bic\u00eatre France"},{"name":"French National Reference Center for Rare Neuropathies (NNERF)  Le Kremlin Bic\u00eatre France"},{"name":"Inserm U1195 &amp; Paris\u2010Saclay University  Le Kremlin Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavi\u00e8re","family":"Lornage","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC)  Illkirch France"},{"name":"INSERM U1258  Illkirch France"},{"name":"CNRS UMR7104  Illkirch France"},{"name":"Strasbourg University  Illkirch 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