{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:54:08Z","timestamp":1782878048677,"version":"3.54.5"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Limb-girdle muscular dystrophies (LGMD) constitute a heterogeneous group of genetic disorders characterized by progressive muscle weakness and atrophy, predominantly affecting the muscles of the pelvic and shoulder girdles. LGMD R27, linked to biallelic pathogenic variants in the <jats:italic>JAG2<\/jats:italic> gene, was recently described, and to date, only 27 cases has been published in three reports. Here, we present two siblings exhibiting a severe clinical phenotype of LGMD R27, associated with a novel <jats:italic>JAG2<\/jats:italic> homozygous frameshift variant [c.3467_3470dup, p.(Pro1158AlafsTer22)] results in truncated protein with 21 amino acid substitution within the cytoplasmic domain of the Jagged2 protein.<\/jats:p>","DOI":"10.3389\/fped.2024.1414465","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T04:45:54Z","timestamp":1732250754000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case Report: Exploring the clinical spectrum of LGMD R27: insights from a case study with homozygous pathogenic variant in the JAG2 gene"],"prefix":"10.3389","volume":"12","author":[{"given":"Sergey","family":"Nikitin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeniya","family":"Melnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Sharkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysylu","family":"Murtazina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Shchagina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoriia","family":"Zabnenkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Tsargush","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Dadali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Kutsev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.ajhg.2021.03.020","article-title":"A form of muscular dystrophy associated with pathogenic variants in JAG2","volume":"108","author":"Coppens","year":"2021","journal-title":"Am J Hum Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"S118","DOI":"10.1016\/j.nmd.2023.07.211","article-title":"Novel JAG2 variants in the first identified Dutch patient with limb-girdle muscular dystrophy R27 and a neuropsychiatric phenotype","volume":"33","author":"Schrama","year":"2023","journal-title":"Neuromuscul Disord"},{"key":"B3","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.nmd.2024.07.003","article-title":"Three novel missense variants in two families with JAG2-associated limb-girdle muscular dystrophy","volume":"42","author":"Dofash","year":"2024","journal-title":"Neuromuscul Disord"},{"key":"B4","doi-asserted-by":"publisher","first-page":"6057","DOI":"10.1128\/MCB.17.10.6057","article-title":"Isolation and functional analysis of a cDNA for human Jagged2, a gene encoding a ligand for the Notch1 receptor","volume":"17","author":"Luo","year":"1997","journal-title":"Mol Cell Biol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1002\/mus.27684","article-title":"The Notch signaling pathway in skeletal muscle health and disease","volume":"66","author":"Vargas-Franco","year":"2022","journal-title":"Muscle Nerve"},{"key":"B6","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1006\/geno.1999.6045","article-title":"Characterization, chromosomal localization, and the complete 30-kb DNA sequence of the human Jagged2 (JAG2) gene","volume":"63","author":"Deng","year":"2000","journal-title":"Genomics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1472-6793-11-6","article-title":"JAK\/STAT signaling and human in vitro myogenesis","volume":"11","author":"Trenerry","year":"2011","journal-title":"BMC Physiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"4634","DOI":"10.1242\/jcs.151787","article-title":"Notch directly regulates the cell morphogenesis genes reck, talin and trio in adult muscle progenitors","volume":"127","author":"Pezeron","year":"2014","journal-title":"J Cell Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2964","DOI":"10.1002\/jcp.25730","article-title":"Roles of Notch1 signaling in regulating satellite cell fates choices and postnatal skeletal myogenesis","volume":"232","author":"Shan","year":"2017","journal-title":"J Cell Physiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"ACMG laboratory quality assurance committee. Standards and guidelines for the interpretation of sequence variants a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.ejogrb.2024.04.029","article-title":"Exome sequencing in genuine empty follicle syndrome: novel candidate genes","volume":"297","author":"Lled\u00f3","year":"2024","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"R187","DOI":"10.1530\/REP-16-0689","article-title":"The role of notch signaling in the mammalian ovary","volume":"153","author":"Vanorny","year":"2017","journal-title":"Reproduction"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2024.1414465\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T04:45:58Z","timestamp":1732250758000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2024.1414465\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,22]]},"references-count":12,"alternative-id":["10.3389\/fped.2024.1414465"],"URL":"https:\/\/doi.org\/10.3389\/fped.2024.1414465","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,22]]},"article-number":"1414465"}}