{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T17:05:33Z","timestamp":1767978333957,"version":"3.49.0"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Hereditary spastic paraplegia (HSP) has been reported rarely because of a monoallelic variant in <jats:italic>ERLIN2<\/jats:italic>. The present study aimed at describing a novel autosomal dominant <jats:italic>ERLIN2<\/jats:italic> pedigree in a Chinese family and exploring the possible mechanism of HSP caused by <jats:italic>ERLIN2<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The proband and his family underwent a comprehensive medical history inquiry and neurological examinations. Whole\u2010exome sequencing was performed on the proband, and Sanger sequencing was performed on some family members. HeLa cell lines and mouse primary cortical neurons were used for immunofluorescence (IF) and reverse transcription\u2010PCR (RT\u2010PCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven patients were clinically diagnosed with pure spastic paraplegia in four consecutive generations with the autosomal dominant inheritance model. All patients presented juvenile\u2010adolescent onset and gradually worsening pure HSP phenotype. Whole\u2010exome sequencing of the proband and Sanger sequencing of all available family members identified a novel heterozygous c.212 T&gt;C (p.V71A) variant in exon 8 of the <jats:italic>ERLIN2<\/jats:italic> gene. The c.212 T&gt;C demonstrated a high pathogenic effect score through functional prediction. RT\u2010PCR and IF analysis of overexpressed V71A revealed an altered ER morphology and increased XBP\u20101S mRNA levels, suggesting the activation of ER stress. Overexpression of V71A in primary cultured cortical neurons promoted axon growth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The novel c.212 T&gt;C heterozygous variant in human <jats:italic>ERLIN2<\/jats:italic> caused pure HSP. Moreover, c.212 T&gt;C heterozygous variant in <jats:italic>ERLIN2<\/jats:italic> increased ER stress and affected axonal development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51902","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T07:21:17Z","timestamp":1695799277000},"page":"2139-2148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel autosomal dominant <scp><i>ERLIN2<\/i><\/scp> variant activates endoplasmic reticulum stress in a Chinese <scp>HSP<\/scp> family"],"prefix":"10.1002","volume":"10","author":[{"given":"Juan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology First Hospital of Shanxi Medical University  Taiyuan China"},{"name":"First Clinical Medical College, Shanxi Medical University  Taiyuan 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