{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:55:54Z","timestamp":1781650554470,"version":"3.54.5"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100011724","name":"Muscular Dystrophy UK","doi-asserted-by":"publisher","award":["25GRO-PG12-0865-1"],"award-info":[{"award-number":["25GRO-PG12-0865-1"]}],"id":[{"id":"10.13039\/100011724","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","award":["SGCL033\\1116"],"award-info":[{"award-number":["SGCL033\\1116"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Neuromuscular Study Group"},{"DOI":"10.13039\/501100003840","name":"Irish Institute of Clinical Neuroscience","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003840","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurogenetics"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Congenital myasthenic syndromes (CMS) are genetically heterogeneous disorders in which precise molecular diagnosis is essential for management. Pathogenic variants in\n                    <jats:italic>PLEC<\/jats:italic>\n                    are a rare cause of autosomal recessive CMS and are frequently associated with epidermolysis bullosa simplex (EBS). We report an adult-onset case with EBS from birth, upper limb\u2013predominant weakness, combined myopathic and myasthenic features, and subtle cardiomyopathy. Initial CMS gene panel testing identified a heterozygous canonical splice-site variant in\n                    <jats:italic>PLEC<\/jats:italic>\n                    . Subsequent trio exome sequencing revealed a second heterozygous intronic variant in trans, and RNA analysis demonstrated intron retention resulting in a frameshift, enabling variant reclassification and definitive diagnosis. This case expands the phenotypic spectrum of\n                    <jats:italic>PLEC<\/jats:italic>\n                    -related disease and highlights the value of transcript-level analysis in resolving cryptic Mendelian disorders.\n                  <\/jats:p>","DOI":"10.1007\/s10048-026-00900-8","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T06:45:59Z","timestamp":1776494759000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adult-onset PLEC-related congenital myasthenic syndrome-myopathy overlap with upper limb predominant weakness"],"prefix":"10.1007","volume":"27","author":[{"given":"Angel","family":"Jose","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aina Jasrul","family":"Azily","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Doyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Stals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Lees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caoimhe","family":"McKenna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy Jayne","family":"McKnight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"McConville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"McMacken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"900_CR1","doi-asserted-by":"publisher","unstructured":"Ohno K, Ito M, Ohkawara B (2025) Review of 40 genes causing congenital myasthenic syndromes. J Hum Genet 1\u201310. https:\/\/doi.org\/10.1038\/s10038-025-01355-9","DOI":"10.1038\/s10038-025-01355-9"},{"issue":"1","key":"900_CR2","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s00401-012-1026-0","volume":"125","author":"L Winter","year":"2013","unstructured":"Winter L, Wiche G (2013) The many faces of plectin and plectinopathies: pathology and mechanisms. Acta Neuropathol (Berl) 125(1):77\u201393. https:\/\/doi.org\/10.1007\/s00401-012-1026-0","journal-title":"Acta Neuropathol (Berl)"},{"issue":"25","key":"900_CR3","doi-asserted-by":"publisher","first-page":"4130","DOI":"10.1091\/mbc.E14-06-1174","volume":"25","author":"E Mihailovska","year":"2014","unstructured":"Mihailovska E, Raith M, Valencia RG, Fischer I, Banchaabouchi MA, Herbst R et al (2014) Neuromuscular synapse integrity requires linkage of acetylcholine receptors to postsynaptic intermediate filament networks via rapsyn\u2013plectin 1f complexes. 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Neuromuscul Disord 20(11):709\u201311. https:\/\/doi.org\/10.1016\/j.nmd.2010.06.003","journal-title":"Neuromuscul Disord"},{"issue":"5","key":"900_CR6","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1111\/j.1399-0004.2010.01602.x","volume":"80","author":"RA Maselli","year":"2011","unstructured":"Maselli RA, Arredondo J, Cagney O, Mozaffar T, Skinner S, Yousif S et al (2011) Congenital myasthenic syndrome associated with epidermolysis bullosa caused by homozygous mutations in PLEC1 and CHRNE. 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