{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:50:53Z","timestamp":1781585453670,"version":"3.54.5"},"reference-count":54,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T00:00:00Z","timestamp":1696204800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T00:00:00Z","timestamp":1696204800000},"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":["Annals of Neurosciences"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Juvenile amyotrophic lateral sclerosis (JALS) is a rare and severe form of motor neuron disease characterized by progressive loss of upper and lower motor neurons with an early onset (&lt;25 years).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Due to complex etiology and clinical heterogeneity, it is indispensable to unravel molecular mechanisms underlying JALS pathology. The study aimed to identify disease-specific signatures in a 14-years-old sporadic JALS patient.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genomic, transcriptomic, and metabolomic analysis of proband and first-degree relatives (FDR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Exome sequencing identified a novel\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      frameshift variation (c.1465dupG: p.D490Gfs*26) in the fused in sarcoma (FUS) gene in proband. Interestingly, rare and potentially deleterious, disease-modifying variations in DDHD domain containing 1 (DDHD1) and fibrillin 2 (FBN2) were observed. Differentially expressed genes (DGEs) enriched in neuromuscular transmission and inflammatory response were identified by RNA-sequencing. In addition, alterations in purine and pyrimidine, vitamin B6, and sphingolipid metabolism reflect the involvement of inflammatory process in disease pathobiology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest the involvement of multiple genetic factors coupled with hampered neuromuscular transmission and systemic inflammation in the onset and disease course of JALS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09727531231194399","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:54:35Z","timestamp":1696294475000},"page":"78-89","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Multiomics Approach Reveal Novel Insights in FUS Driven Juvenile Amyotrophic Lateral Sclerosis: A Family Quartet 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