{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T17:29:13Z","timestamp":1767979753872,"version":"3.49.0"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Hereditary spastic paraplegia (HSP) due to <jats:italic>ERLIN2<\/jats:italic> gene mutations was designated as spastic paraplegia 18 (SPG18). To date, SPG18 families\/cases are still rarely reported. All early reported cases shared the autosomal recessive (AR) inheritance pattern. Over the past 3 years, autosomal dominant (AD) or sporadic SPG18 cases had been continuously reported. Here, we reported the clinical and genetic features of the first autosomal dominant SPG18 pedigree in Chinese.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted detailed medical history inquiry, neurological examinations of the proband and his family members, and charted the family tree. The proband underwent brain and cervical magnetic resonance imaging (MRI), electromyography (EMG), and whole exome sequencing. Sanger sequencing was performed to verify the genetic variation in the proband and some family members. A literature review of all reported SPG18 families\/cases was carried out to summarize the clinical\u2010genetic characteristics of SPG18 under different inheritance patterns.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four patients were clinically diagnosed as chronic spastic paraplegia in three consecutive generations with the autosomal dominant inheritance model. All the patients presented juvenile\u2010adolescent onset and gradually worsening pure HSP phenotype. Clinical phenotypes were consistent within the family. Whole exome sequencing in the proband identified a previously reported heterozygous c.502G\u00a0&gt;\u00a0A (p.V168M) mutation in exon 8 of <jats:italic>ERLIN2<\/jats:italic> gene. This mutation was cosegregated with the phenotype in the family and was classified as likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines. To date, eight AR\u2010SPG18 families, five AD\u2010SPG18 families, and three sporadic cases had been reported. Clinical phenotype of AD\u2010SPG18 was juvenile\u2010adolescent onset pure HSP, while the phenotype of AR\u2010SPG18 was mostly complicated HSP with earlier onset and more severe conditions. In rare cases, the initial spastic paraplegia could evolve to rapidly progressive amyotrophic lateral sclerosis (ALS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We reported the first autosomal dominant SPG18 pedigree in Chinese Han population, which added more pathogenic evidence for V168M mutation. As more SPG18 cases reported, the essentials of SPG18 need to be updated in clinical practice. Special attentions should be given in gene test for upper motor neuron disorders in case of missing heterozygous mutations in <jats:italic>ERLIN2<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.2395","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T05:39:05Z","timestamp":1636004345000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["More autosomal dominant SPG18 cases than recessive? The first AD\u2010SPG18 pedigree in Chinese and literature review"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3207-718X","authenticated-orcid":false,"given":"Shuai","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology Zhengzhou University People's Hospital (Henan Provincial People's Hospital)  Zhengzhou China"},{"name":"Department of Neurology Henan University People's Hospital  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin\u2010Long","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Neurology Zhengzhou University People's Hospital (Henan Provincial People's Hospital)  Zhengzhou China"},{"name":"Department of Neurology Henan University People's Hospital  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology Zhengzhou University People's Hospital (Henan Provincial People's Hospital)  Zhengzhou China"},{"name":"Department of Neurology Henan University People's Hospital  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Zhengzhou University People's Hospital (Henan Provincial People's Hospital)  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie\u2010Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Zhengzhou University People's Hospital (Henan Provincial People's Hospital)  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu\u2010Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Zhengzhou University People's Hospital (Henan Provincial People's Hospital)  Zhengzhou China"},{"name":"Department of Neurology Henan University People's Hospital  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-011-0291-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23641"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000374"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-019-0930-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03060"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.251983"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247363"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-60374-y"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13625"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-021-01099-x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51007"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/0366-6999.193444"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-018-0107-5"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12620-9"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2012.10.003"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01529"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.655043"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3213"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr070"}],"container-title":["Brain 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