{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:20:34Z","timestamp":1777519234243,"version":"3.51.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:00:00Z","timestamp":1606348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100006662","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mutations in the fukutin-related protein gene, FKRP, are the most frequent single cause of \u03b1-dystroglycanopathy. Rare FKRP mutations are clinically not well characterized. Here, we review the phenotype associated with the rare c.919T&amp;gt;A mutation in FKRP in humans and mice. We describe clinical and paraclinical findings in 6 patients, 2 homozygous, and 4-compound heterozygous for c.919T&amp;gt;A, and compare findings with a mouse model we generated, which is homozygous for the same mutation. In patients, the mutation at the homozygous state is associated with a severe congenital muscular dystrophy phenotype invariably characterized by severe multisystem disease and early death. Compound heterozygous patients have a severe limb-girdle muscular dystrophy phenotype, loss of ambulation before age 20 and respiratory insufficiency. In contrast, mice homozygous for the same mutation show no symptoms or signs of muscle disease. Evidence therefore defines the FKRP c.919T&amp;gt;A as a very severe mutation in humans. The huge discrepancy between phenotypes in humans and mice suggests that differences in protein folding\/processing exist between human and mouse Fkrp. This emphasizes the need for more detailed structural analyses of FKRP and shows the challenges of developing appropriate animal models of dystroglycanopathies that mimic the disease course in humans.<\/jats:p>","DOI":"10.1093\/jnen\/nlaa120","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T02:15:14Z","timestamp":1602641714000},"page":"1257-1264","source":"Crossref","is-referenced-by-count":7,"title":["Phenotypic Spectrum of \u03b1-Dystroglycanopathies Associated With the c.919T&amp;gt;a Variant in the <i>FKRP<\/i> Gene in Humans and Mice"],"prefix":"10.1093","volume":"79","author":[{"given":"Susan C","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Royal Veterinary College , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Fernandez-Fuente","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Royal Veterinary College , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital, London, UK and National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health , London"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6144-8544","authenticated-orcid":false,"given":"John","family":"Vissing","sequence":"additional","affiliation":[{"name":"Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen , Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,11,26]]},"reference":[{"key":"2024032523354671000_nlaa120-B1","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1093\/brain\/awm212","article-title":"Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan","volume":"130","author":"Godfrey","year":"2007","journal-title":"Brain J Neurol"},{"key":"2024032523354671000_nlaa120-B2","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.nmd.2012.05.016","article-title":"The inside and out of dystroglycan post-translational modification","volume":"22","author":"Moore","year":"2012","journal-title":"Neuromuscul Disord"},{"key":"2024032523354671000_nlaa120-B3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.matbio.2009.03.003","article-title":"Functional diversity of 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