{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:56:59Z","timestamp":1753869419542,"version":"3.41.2"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC1000306","2005DKA32408"],"award-info":[{"award-number":["2016YFC1000306","2005DKA32408"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81371499"],"award-info":[{"award-number":["81371499"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The dysferlin gene or the <jats:italic>DYSF<\/jats:italic> gene encodes the Ca<jats:sup>2+<\/jats:sup>\u2010dependent phospholipid\u2010binding protein dysferlin, which belongs to the ferlin family and is associated with muscle membrane regeneration and repair. Variants in the <jats:italic>DYSF<\/jats:italic> gene are responsible for limb\u2010girdle muscular dystrophy type 2B (LGMD2B), also called limb\u2010girdle muscular dystrophy recessive 2 (LGMDR2), a rare subtype of muscular dystrophy involving progressive muscle weakness and atrophy. The present study aimed to identify the variants responsible for the clinical symptoms of a Chinese patient with limb girdle muscular dystrophies (LGMDs) and to explore the genotype\u2013phenotype associations of LGMD2B.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A series of clinical examinations, including blood tests, magnetic resonance imaging scans for the lower legs, electromyography and muscle biopsy, was performed on the proband diagnosed with muscular dystrophies. Whole exome sequencing was conducted to detect the causative variants, followed by Sanger sequencing to validate these variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified two compound heterozygous variants in the <jats:italic>DYSF<\/jats:italic> gene, c.1058 T&gt;C, p.(Leu353Pro) in exon 12 and c.1461C&gt;A\/p.Cys487* in exon 16 in this proband, which were inherited from the father and mother, respectively. <jats:italic>In silico<\/jats:italic> analysis for these variants revealed deleterious results by PolyPhen\u20102 (Polymorphism Phenotyping v2; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/genetics.bwh.harvard.edu\/pph2\/\">http:\/\/genetics.bwh.harvard.edu\/pph2<\/jats:ext-link>), SIFT (Sorting Intolerant From Tolerant; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/sift.bii.a-star.edu.sg\/\">https:\/\/sift.bii.a-star.edu.sg<\/jats:ext-link>), PROVEAN (Protein Variation Effect Analyzer; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/provean.jcvi.org\/seq_submit.php\">http:\/\/provean.jcvi.org\/seq_submit.php<\/jats:ext-link>) and MutationTaster (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.mutationtaster.org\/\">http:\/\/www.mutationtaster.org<\/jats:ext-link>). In addition, the two compound heterozygous variants in the proband were absent in 100 control individuals who had an identical ethnic origin and were from the same region, suggesting that these variants may be the pathogenic variants responsible for the LGMD2B phenotypes for this proband.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study broadens our understanding of the mutational spectrum of the <jats:italic>DYSF<\/jats:italic> gene, which provides a deep insight into the pathogenesis of LGMDs and accelerates the development of a prenatal diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3272","type":"journal-article","created":{"date-parts":[[2020,9,5]],"date-time":"2020-09-05T14:04:00Z","timestamp":1599314640000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Compound heterozygous <i>DYSF<\/i> variants causing limb\u2010girdle muscular dystrophy type 2B in a Chinese family"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4500-7412","authenticated-orcid":false,"given":"Liangshan","family":"Li","sequence":"first","affiliation":[{"name":"Medical Genetic Department The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"Department of Clinical Laboratory Medical College of Qingdao University  Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongcui","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenmiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Genetic Department The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinglei","family":"Xu","sequence":"additional","affiliation":[{"name":"Medical Genetic Department The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueping","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Neurology The Affiliated Hospital of Qingdao University  Qingdao 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