{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:46:50Z","timestamp":1791985610409,"version":"4.4.0"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["MDA Award ID: 497263"],"award-info":[{"award-number":["MDA Award ID: 497263"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objectives<\/jats:title>\n \n TUBA4A<\/jats:italic>\n pathogenic variants are associated with ALS, frontotemporal dementia, spastic ataxia, spasticity, ataxia, Parkinson's disease, female infertility, macrothrombocytopenia, and myopathy. Four recently reported patients with\n TUBA4A<\/jats:italic>\n neonatal\/childhood onset myopathy had also a decrement on repetitive nerve stimulation (RNS), but such a finding was not further characterized. We describe a patient with a\n TUBA4A<\/jats:italic>\n pathogenic variant with adulthood\u2010onset genetic myasthenic syndrome accompanied by myopathy and infertility to highlight the neuromuscular junction defect as the main feature of the patient's phenotype.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We reviewed the patient's clinical and laboratory findings and performed transcriptomic analysis on the patient's muscle.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A 53\u2010year\u2010old woman with infertility of unknown etiology manifested fatigability and proximal upper limb muscle weakness in her mid\u201030s, followed by lower limb involvement. Her examination showed proximal muscle weakness and fatigability but spared facial muscles. CK values were mildly elevated. Anti\u2010AChR, MuSK, P\/Q\u2010type calcium channel, and LRP4 antibodies were absent. 2\u2009Hz RNS showed decrement (\u221214% to \u221248%) in limb muscles that improved with 3,4\u2010dyaminopyridine (3,4\u2010DAP). Facilitation (231%) occurred in the trapezius. Muscle biopsy showed patchy loss of oxidative enzyme reactivity and no C5b9 or IgG at neuromuscular junctions. Whole genome sequencing identified a heterozygous known\n TUBA4A<\/jats:italic>\n pathogenic variant (c.850G>A, p.Glu284Lys). Patient improved with 3,4\u2010DAP and albuterol.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n TUBA4A p.Glu284Lys can lead to treatable myasthenic syndrome with postsynaptic and likely presynaptic involvement, as suggested by the patient's electrophysiological findings and response to therapy. This patient expands the\n TUBA4A<\/jats:italic>\n \u2010disorder spectrum to include overlapping myasthenic syndrome\u2010myopathy and shows that neuromuscular disease and infertility can occur within the same patient.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ene.70753","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:07:06Z","timestamp":1789128426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\n TUBA4A<\/i>\n <\/scp>\n Pathogenic Variant Manifesting With Adulthood\u2010Onset Genetic Myasthenic Syndrome, Myopathy,\u00a0and Infertility"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4338-9007","authenticated-orcid":false,"given":"Margherita","family":"Milone","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5631-0559","authenticated-orcid":false,"given":"Stefan","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"},{"name":"Jerry R. Mendell Center for Gene Therapy, Abigail Wexner Research Institute Nationwide Children's Hospital Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6068-5505","authenticated-orcid":false,"given":"Zhiyv","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0212-5697","authenticated-orcid":false,"given":"Teerin","family":"Liewluck","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7773-7754","authenticated-orcid":false,"given":"Eric J.","family":"Sorenson","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Ming","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7488-3705","authenticated-orcid":false,"given":"C. Michael","family":"Harper","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0483-442X","authenticated-orcid":false,"given":"William J.","family":"Litchy","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cm.70044"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26383-9"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201901099"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.09.027"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2023-109786"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awag059"},{"key":"e_1_2_11_8_1","first-page":"lnad032","article-title":"Mutations in TUBA4A Lead to Human Zygotic Arrest and Early Developmental Failure","volume":"2","author":"Li L.","year":"2023","journal-title":"Lifestyle Medicine"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2011.10.009"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26676"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000972"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00257"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2007.01.001"},{"key":"e_1_2_11_14_1","first-page":"1245","article-title":"Increased Acetylation of Microtubules Rescues Human Tau\u2010Induced Microtubule Defects and Neuromuscular Junction Abnormalities in Drosophila","volume":"10","author":"Mao C. 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