{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:39:29Z","timestamp":1760783969493,"version":"3.37.3"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T00:00:00Z","timestamp":1433894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Australian National Health and Medical Research Council Fellowship","award":["APP1002147"],"award-info":[{"award-number":["APP1002147"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:p>Distal myopathies are a group of clinically and pathologically overlapping muscle diseases that are genetically complex and can represent a diagnostic challenge. Laing early\u2010onset distal myopathy (MPD1) is a form of distal myopathy caused by mutations in the <jats:italic>MYH7<\/jats:italic> gene, which encodes the beta myosin heavy chain protein expressed in type 1 skeletal muscle fibers and cardiac myocytes. Here, we present a case of genetically confirmed MPD1 with a typical clinical presentation but distinctive light microscopic and ultrastructural findings on muscle biopsy. A 39\u2010year\u2010old professional male cellist presented with a bilateral foot drop that developed by age 8; analysis of the family pedigree showed an autosomal dominant pattern of inheritance. The physical exam demonstrated bilateral weakness of ankle dorsiflexors, toe extensors and finger extensors; creatine kinase level was normal. Biopsy of the quadriceps femoris muscle showed predominance and hypotrophy of type 1 fibers, hybrid fibers with co\u2010expression of slow and fast myosin proteins (both in highly atrophic and normal size range), moth\u2010eaten fibers and mini\u2010cores, lack of rimmed vacuoles and rare desmin\u2010positive eosinophilic sarcoplasmic inclusions. In addition to these abnormalities often observed in MPD1, the biopsy demonstrated frequent clefted fibers with complex sarcolemmal invaginations; on ultrastructural examination, these structures closely mimicked myotendinous junctions but were present away from the tendon and were almost exclusively found in type 1 fibers. Sequencing analysis of the <jats:italic>MYH7<\/jats:italic> gene in the index patient and other affected family members demonstrated a previously described heterozygous c.4522_4524delGAG (p.Glu1508del) mutation. This case widens the pathologic spectrum of MPD1 and highlights the pathologic and clinical variability that can accompany the same genetic mutation, suggesting a significant role for modifier genes in MPD1 pathogenesis.<\/jats:p>","DOI":"10.1111\/neup.12220","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T14:55:22Z","timestamp":1434725722000},"page":"575-581","source":"Crossref","is-referenced-by-count":6,"title":["Complex sarcolemmal invaginations mimicking myotendinous junctions in a case of Laing early\u2010onset distal myopathy"],"prefix":"10.1111","volume":"35","author":[{"given":"Gerald F.","family":"Reis","sequence":"first","affiliation":[{"name":"Department of Pathology University of California  San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grant","family":"de la Motte","sequence":"additional","affiliation":[{"name":"Palo Alto Medical Foundation  Santa Cruz CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Gooding","sequence":"additional","affiliation":[{"name":"Neurogenetics Unit, PathWest Laboratory Medicine QEII Medical Centre  Nedlands WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel G.","family":"Laing","sequence":"additional","affiliation":[{"name":"Centre for Medical Research, University of Western Australia and Harry Perkins Institute of Medical Research, QEII Medical Centre  Nedlands WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6889-2488","authenticated-orcid":false,"given":"Marta","family":"Margeta","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California  San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2011.10.003"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/424760"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000252808"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10693"},{"key":"e_1_2_7_6_1","first-page":"422","article-title":"Autosomal dominant distal myopathy: linkage to chromosome 14","volume":"56","author":"Laing NG","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22553"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2005.073825"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.02.009"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181eee4d5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-011-5900-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-014-0298-7"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2012.03.003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.05.010"},{"key":"e_1_2_7_15_1","first-page":"53","article-title":"The development of the myotendinous junction. A review","volume":"2","author":"Charvet B","year":"2012","journal-title":"Muscles Ligaments Tendons J"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688503"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1679\/aohc1950.25.275"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/sms.12221"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00310184"}],"container-title":["Neuropathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fneup.12220","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.12220","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T22:17:40Z","timestamp":1696198660000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/neup.12220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,10]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1111\/neup.12220"],"URL":"https:\/\/doi.org\/10.1111\/neup.12220","archive":["Portico"],"relation":{},"ISSN":["0919-6544","1440-1789"],"issn-type":[{"type":"print","value":"0919-6544"},{"type":"electronic","value":"1440-1789"}],"subject":[],"published":{"date-parts":[[2015,6,10]]}}}