{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:38:26Z","timestamp":1793263106166,"version":"4.5.0"},"reference-count":25,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:p>\n                    Autosomal recessive Limb-Girdle Muscular Dystrophy type R28 (LGMDR28; OMIM #620375) is one of the most recently identified subtypes of recessive LGMD. To date, 17 affected individuals from eight unrelated families have been reported to harbor biallelic variants in the\n                    <jats:italic toggle=\"yes\">HMGCR<\/jats:italic>\n                    gene. Here, we report eleven individuals from six unrelated Middle Eastern families diagnosed with LGMDR28 and carrying homozygous variants in\n                    <jats:italic toggle=\"yes\">HMGCR<\/jats:italic>\n                    . Our cohort recapitulated most of the previously described clinical features of the HMGCR-related phenotype. In addition, we also report a family with congenital onset of the condition as well as two affected individuals with liver failure. Through genome and exome sequencing, we identified three novel homozygous missense variants; c.2519G\u2009&gt;A, p.(Arg840Gln), c.1784G\u2009&gt;A, p.(Arg595His), and c.1783C&gt;T, p.(Arg595Cys) and a homozygous in-frame deletion (c.1522_1524del, p.(Ser508del)) previously reported in compound heterozygous state with a second relevant variant and very recently as homozygous in an unrelated proband. This study consolidates the pathogenic role of\n                    <jats:italic toggle=\"yes\">HMGCR<\/jats:italic>\n                    in LGMDR28 while expanding the phenotypic and mutations spectrum of LGMDR28.\n                  <\/jats:p>","DOI":"10.1177\/22143602261436296","type":"journal-article","created":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T22:01:13Z","timestamp":1774821673000},"page":"1303-1312","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Expanded clinical and genetic characterization of autosomal recessive HMGCR-related muscular dystrophy"],"prefix":"10.1177","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2456-0905","authenticated-orcid":false,"given":"Stephany","family":"El-Hayek","sequence":"first","affiliation":[{"name":"Centre for Arab Genomic Studies, Hamdan bin Rashid Foundation for Medical and Educational Sciences, Dubai, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aboulfazl","family":"Rad","sequence":"additional","affiliation":[{"name":"Arcensus GmbH, Rostock 18119, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6973-4809","authenticated-orcid":false,"given":"Sahar","family":"Sedighzadeh","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Sciences, Shahid Chamran University of Ahvaz, Khuzestan, Iran"},{"name":"Dr. Shahrooei Lab, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gozde","family":"Yesil","sequence":"additional","affiliation":[{"name":"Istanbul University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Sabbagh","sequence":"additional","affiliation":[{"name":"Division of Neuro-Pediatrics, Hotel-Dieu de France Hospital, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Shahrooei","sequence":"additional","affiliation":[{"name":"Dr. Shahrooei Lab, Tehran, Iran"},{"name":"Department of Microbiology, Immunology, and Transplantation, Clinical and Diagnostic Immunology, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratibha","family":"Nair","sequence":"additional","affiliation":[{"name":"Centre for Arab Genomic Studies, Hamdan bin Rashid Foundation for Medical and Educational Sciences, Dubai, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuman","family":"Gedikba\u015f\u0131","sequence":"additional","affiliation":[{"name":"Istanbul Medical Faculty"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Bizzari","sequence":"additional","affiliation":[{"name":"Centre for Arab Genomic Studies, Hamdan bin Rashid Foundation for Medical and Educational Sciences, Dubai, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7105-8096","authenticated-orcid":false,"given":"Murtadha","family":"Ali","sequence":"additional","affiliation":[{"name":"Arcensus GmbH, Rostock 18119, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6257-6609","authenticated-orcid":false,"given":"Eliane","family":"Chouery","sequence":"additional","affiliation":[{"name":"Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cybel","family":"Mehawej","sequence":"additional","affiliation":[{"name":"Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayca","family":"Aslanger","sequence":"additional","affiliation":[{"name":"Istanbul University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pejman","family":"Rohani","sequence":"additional","affiliation":[{"name":"Tehran University of Medical Science"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meisam","family":"Sharifzadeh","sequence":"additional","affiliation":[{"name":"Department of Pediatric Intensive Care, Children Medical Center Tehran University of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1510-8817","authenticated-orcid":false,"given":"Sinan","family":"Akbas","sequence":"additional","affiliation":[{"name":"Istanbul University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javad","family":"Mohammadi-asl","sequence":"additional","affiliation":[{"name":"Noor-Gene Genetic Laboratory"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdiyeh","family":"Behnam","sequence":"additional","affiliation":[{"name":"Dr. Shahrooei Lab, Tehran, Iran"},{"name":"Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2951-2293","authenticated-orcid":false,"given":"Sandra","family":"Corbani","sequence":"additional","affiliation":[{"name":"Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volkan","family":"Karaman","sequence":"additional","affiliation":[{"name":"Istanbul University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulu\u00e7","family":"Yi\u015f","sequence":"additional","affiliation":[{"name":"Dokuz Eyl\u00fcl University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-2693","authenticated-orcid":false,"given":"Yavuz","family":"Oktay","sequence":"additional","affiliation":[{"name":"Izmir Biomedicine and Genome Center (IBG)"},{"name":"Dokuz Eylul University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ipek","family":"Polat","sequence":"additional","affiliation":[{"name":"Dokuz Eyl\u00fcl University"},{"name":"Dokuz Eylul University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Andoni","family":"Urtizberea","sequence":"additional","affiliation":[{"name":"Institut de Myologie"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-1542","authenticated-orcid":false,"given":"Reza","family":"Maroofian","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5467-5247","authenticated-orcid":false,"given":"Gabriela","family":"Oprea","sequence":"additional","affiliation":[{"name":"Arcensus GmbH, Rostock 18119, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0714-2469","authenticated-orcid":false,"given":"Andre","family":"Megarbane","sequence":"additional","affiliation":[{"name":"Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University"},{"name":"Institut J\u00e9r\u00f4me Lejeune, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12144769"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-016-0089-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.04.006"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2217831120"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.17406"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.23.2821"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706728"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22844"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22981"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad989"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1734-1140(11)70601-6"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kew386"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-17766-9"},{"key":"e_1_3_3_17_2","article-title":"More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy","volume":"56","author":"Tiniakou E","year":"2017","unstructured":"Tiniakou E, Pinal-Fernandez I, Lloyd TE, et al. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology 2017; 56: 787\u2013794.","journal-title":"Rheumatology"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki375"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.5.819"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200199"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-014-2766-4"},{"key":"e_1_3_3_22_2","first-page":"1","article-title":"Clinical genetics revisited: effect of new techniques (next-generation sequencing, comparative genomic hybridization) on previous diagnoses","volume":"7","author":"M\u00e9garban\u00e9 A","year":"2018","unstructured":"M\u00e9garban\u00e9 A. Clinical genetics revisited: effect of new techniques (next-generation sequencing, comparative genomic hybridization) on previous diagnoses. Middle East J Med Genet 2018; 7: 1\u20136.","journal-title":"Middle East J Med Genet"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-019-0474-y"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40909-3"},{"key":"e_1_3_3_25_2","unstructured":"Clingen. Clinical Genome Resource. HMGCR https:\/\/search.clinicalgenome.org\/kb\/genes\/HGNC:5006 (accessed 14 November 2026)."},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.09.065"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/22143602261436296","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/22143602261436296","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/22143602261436296","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:31:13Z","timestamp":1793262673000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/22143602261436296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,29]]},"references-count":25,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1177\/22143602261436296"],"URL":"https:\/\/doi.org\/10.1177\/22143602261436296","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,29]]}}}