{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:03:42Z","timestamp":1785452622573,"version":"3.56.0"},"reference-count":57,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,8,20]],"date-time":"2022-08-20T00:00:00Z","timestamp":1660953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012295","name":"NIHR Newcastle Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012295","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Dysferlinopathy is an autosomal recessive muscular dystrophy, caused by bi\u2010allelic variants in the gene encoding dysferlin (\n                      <jats:italic>DYSF<\/jats:italic>\n                      ). Onset typically occurs in the second to third decade and is characterised by slowly progressive skeletal muscle weakness and atrophy of the proximal and\/or distal muscles of the four limbs. There are rare cases of symptomatic\n                      <jats:italic>DYSF<\/jats:italic>\n                      variant carriers. Here, we report a large family with a dominantly inherited hyperCKaemia and late\u2010onset muscular dystrophy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      Genetic analysis identified a co\u2010segregating novel\n                      <jats:italic>DYSF<\/jats:italic>\n                      variant [NM_003494.4:c.6207del p.(Tyr2070Metfs*4)]. No secondary variants in\n                      <jats:italic>DYSF<\/jats:italic>\n                      or other dystrophy\u2010related genes were identified on whole genome sequencing and analysis of the proband's DNA. Skeletal muscle involvement was milder and later onset than typical dysferlinopathy presentations; these clinical signs manifested in four individuals, all between the fourth and sixth decades of life. All individuals heterozygous for the c.6207del variant had hyperCKaemia. Histological analysis of skeletal muscle biopsies across three generations showed clear dystrophic signs, including inflammatory infiltrates, regenerating myofibres, increased variability in myofibre size and internal nuclei. Muscle magnetic resonance imaging revealed fatty replacement of muscle in two individuals. Western blot and immunohistochemical analysis of muscle biopsy demonstrated consistent reduction of dysferlin staining. Allele\u2010specific quantitative PCR analysis of\n                      <jats:italic>DYSF<\/jats:italic>\n                      mRNA from patient muscle found that the variant, localised to the extreme C\u2010terminus of dysferlin, does not activate post\u2010transcriptional mRNA decay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We propose that this inheritance pattern may be underappreciated and that other late\u2010onset muscular dystrophy cases with mono\u2010allelic\n                      <jats:italic>DYSF<\/jats:italic>\n                      variants, particularly C\u2010terminal premature truncation variants, may represent dominant forms of disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12846","type":"journal-article","created":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T01:44:12Z","timestamp":1660355052000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Identification of a novel heterozygous\n                    <i>DYSF<\/i>\n                    variant in a large family with a dominantly\u2010inherited dysferlinopathy"],"prefix":"10.1111","volume":"48","author":[{"given":"Chiara","family":"Folland","sequence":"first","affiliation":[{"name":"Centre for Medical Research University of Western Australia, Harry Perkins Institute of Medical Research  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Johnsen","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Innovative Therapeutics Murdoch University  Murdoch Western Australia 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