{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:15:30Z","timestamp":1786976130887,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171256"],"award-info":[{"award-number":["82171256"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202051"],"award-info":[{"award-number":["82202051"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U20A20355"],"award-info":[{"award-number":["U20A20355"]}],"id":[{"id":"10.13039\/501100001809","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":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Hereditary spastic paraplegia (HSP) is a genetically heterogeneous disease caused by over 70 genes, with a significant number of patients still genetically unsolved. In this study, we recruited a suspected HSP family characterized by spasticity, developmental delay, ataxia and hypomyelination, and intended to reveal its molecular etiology by whole exome sequencing (WES) and long\u2010read sequencing (LRS) analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>WES was performed on 13 individuals of the family to identify the causative mutations, including analyses of SNVs (single\u2010nucleotide variants) and CNVs (copy number variants). Accurate circular consensus (CCS) long\u2010read sequencing (LRS) was used to verify the findings of CNV analysis from WES.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SNVs analysis identified a missense variant c.195G&gt;T (p.E65D) of\n                      <jats:italic>MORF4L2<\/jats:italic>\n                      at Xq22.2 co\u2010segregating in this family from WES data. Further CNVs analysis revealed a microdeletion, which was adjacent to the\n                      <jats:italic>MORF4L2<\/jats:italic>\n                      gene, also co\u2010segregating in this family. LRS verified this microdeletion and confirmed the deletion range (chrX: 103,690,507\u2013103,715,018, hg38) with high resolution at nucleotide level accuracy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretations<\/jats:title>\n                    <jats:p>\n                      In this study, we identified an Xq22.2 microdeletion (about 24.5\u2009kb), which contains distal enhancers of the\n                      <jats:italic>PLP1<\/jats:italic>\n                      gene, as a likely cause of SPG2 in this family. The lack of distal enhancers may result in transcriptional repression of\n                      <jats:italic>PLP1<\/jats:italic>\n                      in oligodendrocytes, potentially affecting its role in the maintenance of myelin, and causing SPG2 phenotype. This study has highlighted the importance of noncoding genomic alterations in the genetic etiology of SPG2.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.51848","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T02:22:47Z","timestamp":1689906167000},"page":"1590-1602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Microdeletion in distal\n                    <scp>\n                      <i>PLP1<\/i>\n                    <\/scp>\n                    enhancers causes hereditary spastic paraplegia 2"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7325-5720","authenticated-orcid":false,"given":"Xun","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Geriatric Neurology, Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8189-192X","authenticated-orcid":false,"given":"Yige","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runcheng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University  Changsha China"},{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University  Changsha 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