{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:04:01Z","timestamp":1790071441664,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["310378\/2021\u20104"],"award-info":[{"award-number":["310378\/2021\u20104"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","award":["FE\u2010CLI\u201024\u20100005\u201005"],"award-info":[{"award-number":["FE\u2010CLI\u201024\u20100005\u201005"]}],"id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hereditary motor neuropathies (HMN) represent a heterogeneous group of disorders with wide clinical and genetic variability. Despite advances in molecular diagnostics, approximately 50% of cases remain genetically unresolved, particularly those where distinguishing length\u2010dependent motor neuropathy from motor neuron disorder with disproportionate segmental involvement is a challenge. Variants in the VRK1 gene, originally described in association with pontocerebellar hypoplasia, are now known to produce a broad clinical spectrum, including amyotrophic lateral sclerosis, dHMN, and less frequently, spastic paraplegia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study's aim was to characterize the clinical presentation, electrophysiological findings, and muscle MRI patterns associated with VRK1\u2010related motor neuron disease in a cohort of nine patients from five unrelated families.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Five unrelated families with inherited motor neuropathy were investigated using next\u2010generation sequencing techniques, including targeted gene panels or whole\u2010exome sequencing, with subsequent confirmation by Sanger sequencing. A total of nine affected individuals underwent detailed clinical evaluation, nerve conduction studies (NCS), electromyography (EMG), and whole\u2010body muscle MRI (wbMRI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nine affected individuals carrying biallelic VRK1 variants were evaluated. In most cases (66%), symptom onset occurred during the first decade of life. All patients presented with gradually progressive distal muscle weakness. Mean Medical Research Council (MRC) scores were 2.8 for ankle dorsiflexion and 1.9 for plantar flexion. Sensory nerve conduction studies were normal in all individuals evaluated (8\/9), although mild sensory complaints were reported in four patients. Muscle cramps were observed in two\u2010thirds of the cohort, while fasciculations were uncommon (11%). EMG findings consistently demonstrated a neurogenic pattern with predominant distal involvement, and evidence of both acute and chronic denervation was present in four patients. Whole\u2010body muscle MRI, available for all patients, revealed a consistent pattern of fatty infiltration predominantly affecting posterior muscle compartments, with minimal STIR signal changes. Brain and spinal imaging, performed in all individuals, showed no abnormalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretations<\/jats:title>\n                    <jats:p>Biallelic mutations in VRK1 are associated with a recognizable form of motor neuron disease characterized by features of dHMN combined with upper motor neuron involvement, along with a distinctive posterior\u2010predominant pattern on muscle MRI. Identifying this phenotype, a known presentation of VRK1\u2010related disorders, highlights the importance of targeted genetic testing in unresolved cases of hereditary motor neuropathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jns.70145","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:03:21Z","timestamp":1784088201000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>\n                      <i>VRK1<\/i>\n                    <\/scp>\n                    \u2010Related Motor Neuropathy With Upper Motor Neuron Signs and Selective Muscle Involvement"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6121-5907","authenticated-orcid":false,"given":"Manoella Guerra","family":"de Albuquerque Bueno","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Behavioral Sciences, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3807-9987","authenticated-orcid":false,"given":"Diogo Fernandes","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Clinical Hospital Federal University of Uberl\u00e2ndia (HC\/UFU)  Uberl\u00e2ndia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4648-2896","authenticated-orcid":false,"given":"Alexander M.","family":"Rossor","sequence":"additional","affiliation":[{"name":"MRC Centre for Neuromuscular Diseases National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology, Queen Square  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-8676","authenticated-orcid":false,"given":"Matilde","family":"Laura","sequence":"additional","affiliation":[{"name":"MRC Centre for Neuromuscular Diseases National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology, Queen Square  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2120-2213","authenticated-orcid":false,"given":"Alejandro","family":"Horga","sequence":"additional","affiliation":[{"name":"MRC Centre for Neuromuscular Diseases National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology, Queen Square  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4325-3414","authenticated-orcid":false,"given":"Rodrigo Siqueira Soares","family":"Frezatti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Behavioral Sciences, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo 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