{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:02:37Z","timestamp":1785240157651,"version":"3.55.0"},"reference-count":12,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"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":["497263"],"award-info":[{"award-number":["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":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Agrin\u2010congenital myasthenic syndrome (\n AGRN<\/jats:italic>\n \u2010CMS) is a rare, heterogeneous genetic disorder of the neuromuscular transmission that can present from infancy to adulthood. The clinical phenotype includes distal weakness mimicking distal myopathies. Additionally, electromyography and muscle biopsy may demonstrate myopathic features, increasing the diagnostic challenge. Mitochondrial dysfunction has not been reported in the muscle of\n AGRN<\/jats:italic>\n \u2010CMS patients.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We report the clinical, electrophysiological, radiological, myopathological, and genetic findings of a patient with\n AGRN\u2010<\/jats:italic>\n CMS.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A 47\u2010year\u2010old male presented at age 18 with sudden onset of eyelid ptosis, weakness, and fatigue, followed by dysphagia, dyspnea on exertion, exercise intolerance, and myalgias. Three sisters had similar symptoms. Neurological examination showed lower limb weakness, predominantly affecting the calf muscles with associated atrophy. Tendon reflexes were normal but absent at the ankles. Creatine kinase levels were normal. Electromyography demonstrated myopathic changes in distal muscles with fibrillation potentials in the gastrocnemius. 2\u2009Hz\u2010Repetitive nerve stimulation of the fibular nerve revealed a 32% decrement in the extensor digitorum brevis without facilitation. Tibialis anterior biopsy showed non\u2010specific myopathic changes, neurogenic features, and histological evidence of mitochondrial dysfunction, as suggested by the scattered cytochrome c oxidase\u2010negative fibers. Whole exome sequencing detected a homozygous pathogenic\n AGRN<\/jats:italic>\n variant (c.5012G>A, p.Arg1671Gln). No pathogenic or suspected pathogenic variants were detected in muscle mitochondrial DNA or in nuclear genes affecting mitochondrial function.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This patient expands the pathological spectrum of\n AGRN<\/jats:italic>\n \u2010CMS to include mitochondrial dysfunction and highlights the importance of low\u2010frequency repetitive nerve stimulation in the assessment of patients with distal weakness for differentiating myopathies from CMS.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ene.70690","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T09:52:48Z","timestamp":1782726768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distal Agrin (\n \n AGRN<\/i>\n <\/scp>\n ) Congenital Myasthenic Syndrome With Mitochondrial Dysfunction"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-9100","authenticated-orcid":false,"given":"Mariana Manoel","family":"Oku","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyv","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duygu","family":"Selcen","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Litchy","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4338-9007","authenticated-orcid":false,"given":"Margherita","family":"Milone","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.06.015"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu160"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010025\u201001355\u20109"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51346"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000393"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.246710"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12093308"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm6070064"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-140021"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-019-0506-2"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36277-7"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24108505"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.70690","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ene.70690","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.70690","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:20:51Z","timestamp":1785237651000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.70690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":12,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/ene.70690"],"URL":"https:\/\/doi.org\/10.1111\/ene.70690","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]},"assertion":[{"value":"2026-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70690"}}