{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:01:54Z","timestamp":1780632114330,"version":"3.54.1"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T00:00:00Z","timestamp":1569542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Motor neuron disorders involving upper and lower neurons are a genetically and clinically heterogenous group of rare neuromuscular disorders with overlap among spinal muscular atrophies (SMAs) and amyotrophic lateral sclerosis (ALS). Classical SMA caused by recessive mutations in <jats:italic>SMN1<\/jats:italic> is one of the most common genetic causes of mortality in infants. It is characterized by degeneration of anterior horn cells in the spinal cord, leading to progressive muscle weakness and atrophy. Non\u2010SMN1\u2010related spinal muscular atrophies are caused by variants in a number of genes, including <jats:italic>VRK1<\/jats:italic>, encoding the vaccinia\u2010related kinase 1 (VRK1). <jats:italic>VRK1<\/jats:italic> variants have been segregated with motor neuron diseases including SMA phenotypes or hereditary complex motor and sensory axonal neuropathy (HMSN), with or without pontocerebellar hypoplasia or microcephaly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we report an association of a novel homozygous splice variant in <jats:italic>VRK1<\/jats:italic> (c.1159\u00a0+\u00a01G&gt;A) with childhood\u2010onset SMA or juvenile lower motor disease with brisk tendon reflexes without pontocerebellar hypoplasia and normal intellectual ability in a family with five affected individuals. We show that the <jats:italic>VRK1<\/jats:italic> splice variant in patients causes decreased splicing efficiency and a mRNA frameshift that escapes the nonsense\u2010mediated decay machinery and results in a premature termination codon.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings unveil the impact of the variant on the <jats:italic>VRK1<\/jats:italic> transcript and further support the implication of <jats:italic>VRK1<\/jats:italic> in the pathogenesis of lower motor neuron diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50912","type":"journal-article","created":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T10:02:11Z","timestamp":1569578531000},"page":"2197-2204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Motor neuron diseases caused by a novel <i>VRK1<\/i> variant \u2013 A genotype\/phenotype study"],"prefix":"10.1002","volume":"6","author":[{"given":"Maryam","family":"Sedghi","sequence":"first","affiliation":[{"name":"Medical Genetics Laboratory Alzahra University Hospital Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali\u2010Reza","family":"Moslemi","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Gothenburg Sahlgrenska University Hospital Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montse","family":"Olive","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology Department of Pathology Institut Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL)\u2010Hospital de Bellvitge Hospitalet de Llobregat 08907 Barcelona Spain"},{"name":"Neuromuscular Unit Department of Neurology Institut Investigaci\u00f3 Biom\u00e8dica de Bellvitge\u2010(IDIBELL)\u2010Hospital de Bellvitge Hospitalet de Llobregat 08907 Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud","family":"Etemadifar","sequence":"additional","affiliation":[{"name":"Department of Functional Neursurgery Faculty of Medicine Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behnaz","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculty of Medicine Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jafar","family":"Nasiri","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Faculty of Medicine Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Emrahi","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Gothenburg Sahlgrenska University Hospital Gothenburg 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Medicine University of Skovde Skovde Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90460-3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10897-016-9955-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(02)00211-0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0387-7604(93)90080-R"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.10863"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1998-14.2015"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.07.006"},{"key":"e_1_2_9_9_1","first-page":"1491","article-title":"Mutations in VRK1 associated with complex motor and sensory axonal neuropathy plus microcephaly","volume":"70","author":"Gonzaga\u2010Jauregui 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