{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T22:25:19Z","timestamp":1767651919267,"version":"3.41.2"},"reference-count":24,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,7,28]],"date-time":"2024-07-28T00:00:00Z","timestamp":1722124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["R01HG009141"],"award-info":[{"award-number":["R01HG009141"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013995","name":"Sanofi Genzyme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013220","name":"Ultragenyx Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013220","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013780","name":"Limb Girdle Muscular Dystrophy 2i Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018191","name":"LGMD2D Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011724","name":"Muscular Dystrophy UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011724","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100029087","name":"Bernard F. and Alva B. Gimbel Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100029087","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Heterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene <jats:italic>HNRNPA1<\/jats:italic> has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis\u2010like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of <jats:italic>HNRNPA1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two individuals with unsolved juvenile\u2010onset myopathy were enrolled under approved institutional protocols. Phenotype data were collected and genetic analyses were performed, including whole\u2010exome sequencing (WES).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The two probands (MNOT002\u201001 and K1440\u201001) showed a similar onset of slowly progressive extremity and facial weakness in early adolescence. K1440\u201001 presented with facial weakness, winged scapula, elevated serum creatine kinase (CK) levels, and mild neck weakness. MNOT002\u201001 also exhibited elevated CK levels along with facial weakness, cardiomyopathy, respiratory dysfunction, pectus excavatum, a mildly rigid spine, and loss of ambulation. On quadriceps muscle biopsy, K1440\u201001 displayed rounded myofibers, mild variation in fiber diameter, and type 2 fiber hypertrophy, while MNOT002\u201001 displayed rimmed vacuoles. Monoallelic stop\u2010loss variants in <jats:italic>HNRNPA1<\/jats:italic> were identified for both probands: c.1119A&gt;C p.*373Tyrext*6 (K1440\u201001) and c.1118A&gt;C p.*373Serext*6 (MNOT002\u201001) affect the same codon and are both predicted to lead to the addition of six amino acids before termination at an alternative stop codon.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Both stop\u2010loss variants in our probands are likely pathogenic. Our findings contribute to the disease characterization of pathogenic variants in <jats:italic>HNRNPA1<\/jats:italic>. This gene should be screened in clinical diagnostic testing of unsolved cases of sporadic or dominant juvenile\u2010onset myopathy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28214","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T05:45:25Z","timestamp":1722231925000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dominant stop\u2010loss <i>HNRNPA1<\/i> variants in juvenile\u2010onset myopathy"],"prefix":"10.1002","author":[{"given":"Johnnie","family":"Turner","sequence":"first","affiliation":[{"name":"Greg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8366-3691","authenticated-orcid":false,"given":"Christine C.","family":"Bruels","sequence":"additional","affiliation":[{"name":"Greg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey L.","family":"Daugherty","sequence":"additional","affiliation":[{"name":"Greg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elicia A.","family":"Estrella","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Division of Genetics and Genomics Boston Children's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seth","family":"Stafki","sequence":"additional","affiliation":[{"name":"Greg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Safoora B.","family":"Syeda","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics University of Florida College of Medicine  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah R.","family":"Littel","sequence":"additional","affiliation":[{"name":"Greg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Pais","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Mendelian Genomics, Program in Medical and Population Genetics Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijay S.","family":"Ganesh","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Mendelian Genomics, Program in Medical and Population Genetics Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"},{"name":"Analytic and Translational Genetics Unit and Center for Genomic Medicine, Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Neurology Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hart G. 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