{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T07:14:25Z","timestamp":1773126865747,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471202"],"award-info":[{"award-number":["81471202"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Hereditary spastic paraplegias (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders. We describe the genetic and clinical features of a cohort of five HSP families from central\u2010southern China.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using targeted exome\u2010sequencing technology, we investigated the genetic and clinical features in five HSP families. We reviewed the clinical histories of these patients as well as the molecular and functional characterization of the associated gene variants. We also performed functional analysis of an intron variant of\n                      <jats:italic>SPAST<\/jats:italic>\n                      in vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a known\n                      <jats:italic>SPAST<\/jats:italic>\n                      mutation (p.Pro435Leu) in a family with autosomal dominant HSP (AD\u2010HSP) and four novel variants in two HSP families and a sporadic case. These identified four novel variants included a variant in\n                      <jats:italic>SPG11<\/jats:italic>\n                      (p.Val1979Ter), two variants in\n                      <jats:italic>B4GALNT1<\/jats:italic>\n                      (p.Ser475Phe and c.1002\u00a0+\u00a02\u00a0T\u00a0&gt;\u00a0G), and a splicing site variant in\n                      <jats:italic>SPAST<\/jats:italic>\n                      (c.1245+5G&gt;A). Minigene analysis of the splicing variant in\n                      <jats:italic>SPAST<\/jats:italic>\n                      (c.1245+5G&gt;A) revealed that the mutation resulted in mRNAs with a loss of exon 9. The SPG4 family carrying c.1245+5G&gt;A variant in\n                      <jats:italic>SPAST<\/jats:italic>\n                      exhibited genetic anticipation, with a decreased age at onset and increased severity in successive generations. The proband with p.Val1979Ter variant in\n                      <jats:italic>SPG11<\/jats:italic>\n                      showed characteristic clinical features of early\u2010onset, severe spasticity, and corpus callosum atrophy which were highly suggestive of the diagnosis of SPG11\u2010associated HSP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings strongly support variable phenotype of\n                      <jats:italic>B4GALNT1<\/jats:italic>\n                      \u2010related SPG26 and also expand the clinical and mutation spectrum of HSP caused by mutations in\n                      <jats:italic>SPAST<\/jats:italic>\n                      ,\n                      <jats:italic>SPG11<\/jats:italic>\n                      , and\n                      <jats:italic>B4GALNT1<\/jats:italic>\n                      . These results will help to improve the efficiency of early diagnosis in patients clinically suspected of HSP.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.1627","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T07:43:40Z","timestamp":1614411820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The investigation of genetic and clinical features in patients with hereditary spastic paraplegia in central\u2010Southern China"],"prefix":"10.1002","volume":"9","author":[{"given":"Chen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology Wuhan Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun\u2010Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Wuhan Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ci\u2010Hao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Radiology Wuhan Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De","family":"Li","sequence":"additional","affiliation":[{"name":"Biobank Wuhan Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6252-9477","authenticated-orcid":false,"given":"Zhi\u2010Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Wuhan Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 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