{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:01:23Z","timestamp":1793278883006,"version":"4.5.0"},"reference-count":114,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T00:00:00Z","timestamp":1614470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T00:00:00Z","timestamp":1614470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr Neurol Neurosci Rep"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose of Review<\/jats:title>\n                <jats:p>The hereditary spastic paraplegias (HSPs) are a group of disorders characterised by progressive lower limb weakness and spasticity. We address the challenges and controversies involved in the genetic diagnosis of HSP.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Recent Findings<\/jats:title>\n                <jats:p>There is a large and rapidly expanding list of genes implicated in HSP, making it difficult to keep gene testing panels updated. There is also a high degree of phenotypic overlap between HSP and other disorders, leading to problems in choosing the right panel to analyse. We discuss genetic testing strategies for overcoming these diagnostic hurdles, including the use of targeted sequencing gene panels, whole-exome sequencing and whole-genome sequencing. Personalised treatments for HSP are on the horizon, and a genetic diagnosis may hold the key to access these treatments.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Summary<\/jats:title>\n                <jats:p>Developing strategies to overcome the challenges and controversies in HSP may hold the key to a rapid and accurate genetic diagnosis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11910-021-01099-x","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T10:02:52Z","timestamp":1614592972000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Challenges and Controversies in the Genetic Diagnosis of Hereditary Spastic Paraplegia"],"prefix":"10.1007","volume":"21","author":[{"given":"Lydia","family":"Saputra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3482-6962","authenticated-orcid":false,"given":"Kishore Raj","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,28]]},"reference":[{"issue":"3","key":"1099_CR1","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1002\/mdc3.12184","volume":"2","author":"KR Kumar","year":"2015","unstructured":"Kumar KR, Blair NF, Sue CM. An update on the hereditary spastic paraplegias: new genes and new disease models. Mov Disord Clin Pract. 2015;2(3):213\u201323. https:\/\/doi.org\/10.1002\/mdc3.12184.","journal-title":"Mov Disord Clin Pract"},{"issue":"6","key":"1099_CR2","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1212\/wnl.46.6.1507","volume":"46","author":"JK Fink","year":"1996","unstructured":"Fink JK, Heiman-Patterson T, Bird T, Cambi F, Dube MP, Figlewicz DA, et al. Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working group. Neurology. 1996;46(6):1507\u201314. https:\/\/doi.org\/10.1212\/wnl.46.6.1507.","journal-title":"Neurology"},{"issue":"1-2","key":"1099_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jns.2012.03.025","volume":"318","author":"J Finsterer","year":"2012","unstructured":"Finsterer J, Loscher W, Quasthoff S, Wanschitz J, Auer-Grumbach M, Stevanin G. Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance. J Neurol Sci. 2012;318(1-2):1\u201318. https:\/\/doi.org\/10.1016\/j.jns.2012.03.025.","journal-title":"J Neurol Sci"},{"issue":"4","key":"1099_CR4","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1002\/mds.26527","volume":"31","author":"C Marras","year":"2016","unstructured":"Marras C, Lang A, van de Warrenburg BP, Sue CM, Tabrizi SJ, Bertram L, et al. Nomenclature of genetic movement disorders: recommendations of the international Parkinson and movement disorder society task force. Mov Disord. 2016;31(4):436\u201357. https:\/\/doi.org\/10.1002\/mds.26527.","journal-title":"Mov Disord"},{"issue":"3","key":"1099_CR5","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1159\/000358801","volume":"42","author":"L Ruano","year":"2014","unstructured":"Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014;42(3):174\u201383. https:\/\/doi.org\/10.1159\/000358801.","journal-title":"Neuroepidemiology."},{"issue":"4","key":"1099_CR6","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1086\/514346","volume":"80","author":"VA McKusick","year":"2007","unstructured":"McKusick VA. Mendelian inheritance in man and its online version, OMIM. Am J Hum Genet. 2007;80(4):588\u2013604. https:\/\/doi.org\/10.1086\/514346.","journal-title":"Am J Hum Genet"},{"issue":"8","key":"1099_CR7","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1038\/s10038-018-0463-6","volume":"63","author":"A Das Bhowmik","year":"2018","unstructured":"Das Bhowmik A, Patil SJ, Deshpande DV, Bhat V, Dalal A. Novel splice-site variant of UCHL1 in an Indian family with autosomal recessive spastic paraplegia-79. J Hum Genet. 2018;63(8):927\u201333. https:\/\/doi.org\/10.1038\/s10038-018-0463-6.","journal-title":"J Hum Genet"},{"issue":"4","key":"1099_CR8","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.ajhg.2019.03.001\\","volume":"104","author":"MA Farazi Fard","year":"2019","unstructured":"Farazi Fard MA, Rebelo AP, Buglo E, Nemati H, Dastsooz H, Gehweiler I, et al. Truncating mutations in UBAP1 cause hereditary spastic paraplegia. Am J Hum Genet. 2019;104(4):767\u201373. https:\/\/doi.org\/10.1016\/j.ajhg.2019.03.001\\UBAP1 is an important new gene causing autosomal dominant HSP. It has been identified by numerous groups and probably warrants widespread clinical testing.","journal-title":"Am J Hum Genet"},{"key":"1099_CR9","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1002\/humu.23950","volume":"41","author":"S Gu","year":"2019","unstructured":"Gu S, Chen CA, Rosenfeld JA, Cope H, Launay N, Flanigan KM, et al. Truncating variants in UBAP1 associated with childhood-onset nonsyndromic hereditary spastic paraplegia. Hum Mutat. 2019;41:632\u201340. https:\/\/doi.org\/10.1002\/humu.23950.","journal-title":"Hum Mutat"},{"issue":"8","key":"1099_CR10","doi-asserted-by":"publisher","first-page":"2238","DOI":"10.1093\/brain\/awz158","volume":"142","author":"X Lin","year":"2019","unstructured":"Lin X, Su HZ, Dong EL, Lin XH, Zhao M, Yang C, et al. Stop-gain mutations in UBAP1 cause pure autosomal-dominant spastic paraplegia. Brain. 2019;142(8):2238\u201352. https:\/\/doi.org\/10.1093\/brain\/awz158.","journal-title":"Brain."},{"issue":"11","key":"1099_CR11","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1038\/s10038-019-0670-9","volume":"64","author":"H Nan","year":"2019","unstructured":"Nan H, Ichinose Y, Tanaka M, Koh K, Ishiura H, Mitsui J, et al. UBAP1 mutations cause juvenile-onset hereditary spastic paraplegias (SPG80) and impair UBAP1 targeting to endosomes. J Hum Genet. 2019;64(11):1055\u201365. https:\/\/doi.org\/10.1038\/s10038-019-0670-9.","journal-title":"J Hum Genet"},{"issue":"3","key":"1099_CR12","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1093\/brain\/aww318","volume":"140","author":"MY Ahmed","year":"2017","unstructured":"Ahmed MY, Al-Khayat A, Al-Murshedi F, Al-Futaisi A, Chioza BA, Pedro Fernandez-Murray J, et al. A mutation of EPT1 (SELENOI) underlies a new disorder of Kennedy pathway phospholipid biosynthesis. Brain. 2017;140(3):547\u201354. https:\/\/doi.org\/10.1093\/brain\/aww318.","journal-title":"Brain."},{"issue":"11","key":"1099_CR13","doi-asserted-by":"publisher","first-page":"3382","DOI":"10.1093\/brain\/awz291","volume":"142","author":"FM Vaz","year":"2019","unstructured":"Vaz FM, McDermott JH, Alders M, Wortmann SB, Kolker S, Pras-Raves ML, et al. Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia. Brain. 2019;142(11):3382\u201397. https:\/\/doi.org\/10.1093\/brain\/awz291.","journal-title":"Brain."},{"issue":"1","key":"1099_CR14","doi-asserted-by":"publisher","first-page":"4790","DOI":"10.1038\/s41467-019-12620-9","volume":"10","author":"M Wagner","year":"2019","unstructured":"Wagner M, Osborn DPS, Gehweiler I, Nagel M, Ulmer U, Bakhtiari S, et al. Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia. Nat Commun. 2019;10(1):4790. https:\/\/doi.org\/10.1038\/s41467-019-12620-9RNF170 has now been independly confirmed as a cause of autosomal recessive HSP. Of note, heterozygous mutations in this gene can cause autosomal dominant sensory ataxia 1.","journal-title":"Nat Commun"},{"issue":"2","key":"1099_CR15","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.ajhg.2020.06.015","volume":"107","author":"RA Husain","year":"2020","unstructured":"Husain RA, Grimmel M, Wagner M, Hennings JC, Marx C, Feichtinger RG, et al. Bi-allelic HPDL variants cause a neurodegenerative disease ranging from neonatal encephalopathy to adolescent-onset spastic paraplegia. Am J Hum Genet. 2020;107(2):364\u201373. https:\/\/doi.org\/10.1016\/j.ajhg.2020.06.015.","journal-title":"Am J Hum Genet"},{"key":"1099_CR16","doi-asserted-by":"publisher","unstructured":"Ferdinandusse S, McWalter K, Te Brinke H, Lodewijk IJ, Mooijer PM, Ruiter JPN, et al. An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids. Genet Med. 2020. https:\/\/doi.org\/10.1038\/s41436-020-01027-3.","DOI":"10.1038\/s41436-020-01027-3"},{"issue":"6","key":"1099_CR17","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/j.ajhg.2008.11.003","volume":"83","author":"P Lin","year":"2008","unstructured":"Lin P, Li J, Liu Q, Mao F, Li J, Qiu R, et al. A missense mutation in SLC33A1, which encodes the acetyl-CoA transporter, causes autosomal-dominant spastic paraplegia (SPG42). Am J Hum Genet. 2008;83(6):752\u20139. https:\/\/doi.org\/10.1016\/j.ajhg.2008.11.003.","journal-title":"Am J Hum Genet"},{"issue":"9","key":"1099_CR18","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/ejhg.2010.68","volume":"18","author":"NA Schlipf","year":"2010","unstructured":"Schlipf NA, Beetz C, Schule R, Stevanin G, Erichsen AK, Forlani S, et al. A total of 220 patients with autosomal dominant spastic paraplegia do not display mutations in the SLC33A1 gene (SPG42). Eur J Hum Genet. 2010;18(9):1065\u20137. https:\/\/doi.org\/10.1038\/ejhg.2010.68.","journal-title":"Eur J Hum Genet"},{"issue":"3","key":"1099_CR19","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1002\/mds.26944","volume":"32","author":"M Synofzik","year":"2017","unstructured":"Synofzik M, Schule R. Overcoming the divide between ataxias and spastic paraplegias: Shared phenotypes, genes, and pathways. Mov Disord. 2017;32(3):332\u201345. https:\/\/doi.org\/10.1002\/mds.26944.","journal-title":"Mov Disord"},{"issue":"1","key":"1099_CR20","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s12311-018-0969-7","volume":"18","author":"C Kang","year":"2019","unstructured":"Kang C, Liang C, Ahmad KE, Gu Y, Siow SF, Colebatch JG, et al. High degree of genetic heterogeneity for hereditary cerebellar ataxias in Australia. Cerebellum. 2019;18(1):137\u201346. https:\/\/doi.org\/10.1007\/s12311-018-0969-7.","journal-title":"Cerebellum."},{"issue":"10","key":"1099_CR21","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1007\/s00415-013-7008-x","volume":"260","author":"KR Kumar","year":"2013","unstructured":"Kumar KR, Blair NF, Vandebona H, Liang C, Ng K, Sharpe DM, et al. Targeted next generation sequencing in SPAST-negative hereditary spastic paraplegia. J Neurol. 2013;260(10):2516\u201322. https:\/\/doi.org\/10.1007\/s00415-013-7008-x.","journal-title":"J Neurol"},{"key":"1099_CR22","doi-asserted-by":"publisher","first-page":"820","DOI":"10.3389\/fnins.2020.00820","volume":"14","author":"G Wali","year":"2020","unstructured":"Wali G, Kumar KR, Liyanage E, Davis RL, Mackay-Sim A, Sue CM. Mitochondrial function in hereditary spastic paraplegia: deficits in SPG7 but not SPAST patient-derived stem cells. Front Neurosci. 2020;14:820. https:\/\/doi.org\/10.3389\/fnins.2020.00820.","journal-title":"Front Neurosci"},{"issue":"1","key":"1099_CR23","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1111\/ene.13768","volume":"26","author":"C Mancini","year":"2019","unstructured":"Mancini C, Giorgio E, Rubegni A, Pradotto L, Bagnoli S, Rubino E, et al. Prevalence and phenotype of the c.1529C>T SPG7 variant in adult-onset cerebellar ataxia in Italy. Eur J Neurol. 2019;26(1):80\u20136. https:\/\/doi.org\/10.1111\/ene.13768.","journal-title":"Eur J Neurol"},{"key":"1099_CR24","doi-asserted-by":"publisher","unstructured":"Kim A, Kumar KR, Davis RL, Mallawaarachchi AC, Gayevskiy V, Minoche AE, et al. Increased diagnostic yield of spastic paraplegia with or without cerebellar ataxia through whole-genome sequencing. Cerebellum. 2019. https:\/\/doi.org\/10.1007\/s12311-019-01038-0This study suggests it may be helpful to investigate spastic paraplegia and ataxia as a single disease spectrum or common entity, using WGS to interrogate both HSP and ataxia genes.","DOI":"10.1007\/s12311-019-01038-0"},{"issue":"1","key":"1099_CR25","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.celrep.2016.05.044","volume":"16","author":"Y Wang","year":"2016","unstructured":"Wang Y, Hersheson J, Lopez D, Hammer M, Liu Y, Lee KH, et al. Defects in the CAPN1 gene result in alterations in cerebellar development and cerebellar ataxia in mice and humans. Cell Rep. 2016;16(1):79\u201391. https:\/\/doi.org\/10.1016\/j.celrep.2016.05.044.","journal-title":"Cell Rep"},{"key":"1099_CR26","doi-asserted-by":"publisher","first-page":"103605","DOI":"10.1016\/j.ejmg.2018.12.010","volume":"62","author":"A Shetty","year":"2018","unstructured":"Shetty A, Gan-Or Z, Ashtiani S, Ruskey JA, van de Warrenburg B, Wassenberg T, et al. CAPN1 mutations: expanding the CAPN1-related phenotype: from hereditary spastic paraparesis to spastic ataxia. Eur J Med Genet. 2018;62:103605. https:\/\/doi.org\/10.1016\/j.ejmg.2018.12.010.","journal-title":"Eur J Med Genet"},{"issue":"5","key":"1099_CR27","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.ajhg.2016.04.002","volume":"98","author":"Z Gan-Or","year":"2016","unstructured":"Gan-Or Z, Bouslam N, Birouk N, Lissouba A, Chambers DB, Veriepe J, et al. Mutations in CAPN1 cause autosomal-recessive hereditary spastic paraplegia. Am J Hum Genet. 2016;98(5):1038\u201346. https:\/\/doi.org\/10.1016\/j.ajhg.2016.04.002.","journal-title":"Am J Hum Genet"},{"key":"1099_CR28","doi-asserted-by":"publisher","unstructured":"Nicita F, Ginevrino M, Travaglini L, D\u2019Arrigo S, Zorzi G, Borgatti R, et al. Heterozygous KIF1A variants underlie a wide spectrum of neurodevelopmental and neurodegenerative disorders. J Med Genet. 2020. https:\/\/doi.org\/10.1136\/jmedgenet-2020-107007Recent study showing that heterozygous KIF1A variants can cause both HSP and ataxia phenotypes.","DOI":"10.1136\/jmedgenet-2020-107007"},{"key":"1099_CR29","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1750-1172-8-41","volume":"8","author":"M Synofzik","year":"2013","unstructured":"Synofzik M, Soehn AS, Gburek-Augustat J, Schicks J, Karle KN, Schule R, et al. Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum. Orphanet J Rare Dis. 2013;8:41. https:\/\/doi.org\/10.1186\/1750-1172-8-41.","journal-title":"Orphanet J Rare Dis"},{"issue":"6","key":"1099_CR30","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1002\/ana.25220","volume":"83","author":"E Seong","year":"2018","unstructured":"Seong E, Insolera R, Dulovic M, Kamsteeg EJ, Trinh J, Bruggemann N, et al. Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects. Ann Neurol. 2018;83(6):1075\u201388. https:\/\/doi.org\/10.1002\/ana.25220.","journal-title":"Ann Neurol"},{"issue":"3","key":"1099_CR31","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1108","volume":"8","author":"K Koh","year":"2020","unstructured":"Koh K, Ishiura H, Shimazaki H, Tsutsumiuchi M, Ichinose Y, Nan H, et al. VPS13D-related disorders presenting as a pure and complicated form of hereditary spastic paraplegia. Mol Genet Genomic Med. 2020;8(3):e1108. https:\/\/doi.org\/10.1002\/mgg3.1108.","journal-title":"Mol Genet Genomic Med"},{"issue":"9","key":"1099_CR32","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1002\/humu.22148","volume":"33","author":"C Bettencourt","year":"2012","unstructured":"Bettencourt C, Quintans B, Ros R, Ampuero I, Yanez Z, Pascual SI, et al. Revisiting genotype-phenotype overlap in neurogenetics: triplet-repeat expansions mimicking spastic paraplegias. Hum Mutat. 2012;33(9):1315\u201323. https:\/\/doi.org\/10.1002\/humu.22148.","journal-title":"Hum Mutat"},{"key":"1099_CR33","unstructured":"Ito D BSCL2-related neurologic disorders\/seipinopathy. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al., editors. GeneReviews((R)). Seattle (WA)1993."},{"issue":"1","key":"1099_CR34","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s00415-016-8301-2","volume":"264","author":"T Musacchio","year":"2017","unstructured":"Musacchio T, Zaum AK, Uceyler N, Sommer C, Pfeifroth N, Reiners K, et al. ALS and MMN mimics in patients with BSCL2 mutations: the expanding clinical spectrum of SPG17 hereditary spastic paraplegia. J Neurol. 2017;264(1):11\u201320. https:\/\/doi.org\/10.1007\/s00415-016-8301-2.","journal-title":"J Neurol"},{"issue":"3","key":"1099_CR35","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/ng1980","volume":"39","author":"G Stevanin","year":"2007","unstructured":"Stevanin G, Santorelli FM, Azzedine H, Coutinho P, Chomilier J, Denora PS, et al. Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat Genet. 2007;39(3):366\u201372. https:\/\/doi.org\/10.1038\/ng1980.","journal-title":"Nat Genet"},{"issue":"Pt 1","key":"1099_CR36","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1093\/brain\/awv320","volume":"139","author":"C Montecchiani","year":"2016","unstructured":"Montecchiani C, Pedace L, Lo Giudice T, Casella A, Mearini M, Gaudiello F, et al. ALS5\/SPG11\/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease. Brain. 2016;139(Pt 1):73\u201385. https:\/\/doi.org\/10.1093\/brain\/awv320.","journal-title":"Brain."},{"issue":"6170","key":"1099_CR37","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1126\/science.1247363","volume":"343","author":"G Novarino","year":"2014","unstructured":"Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, Heiberg AD, et al. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 2014;343(6170):506\u201311. https:\/\/doi.org\/10.1126\/science.1247363.","journal-title":"Science."},{"issue":"11","key":"1099_CR38","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1136\/jnnp-2013-305049","volume":"84","author":"M Gonzalez","year":"2013","unstructured":"Gonzalez M, McLaughlin H, Houlden H, Guo M, Yo-Tsen L, Hadjivassilious M, et al. Exome sequencing identifies a significant variant in methionyl-tRNA synthetase (MARS) in a family with late-onset CMT2. J Neurol Neurosurg Psychiatry. 2013;84(11):1247\u20139. https:\/\/doi.org\/10.1136\/jnnp-2013-305049.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1099_CR39","doi-asserted-by":"publisher","unstructured":"de Sainte Agathe JM, Mercier S, Mahe JY, Pereon Y, Buratti J, Tissier L, et al. RNF170-related hereditary spastic paraplegia: confirmation by a novel mutation. Mov Disord. 2020. https:\/\/doi.org\/10.1002\/mds.28371.","DOI":"10.1002\/mds.28371"},{"issue":"11","key":"1099_CR40","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1136\/jnnp-2020-323719","volume":"91","author":"A Cortese","year":"2020","unstructured":"Cortese A, Callegari I, Curro R, Vegezzi E, Colnaghi S, Versino M, et al. Mutation in RNF170 causes sensory ataxic neuropathy with vestibular areflexia: a CANVAS mimic. J Neurol Neurosurg Psychiatry. 2020;91(11):1237\u20138. https:\/\/doi.org\/10.1136\/jnnp-2020-323719.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"5","key":"1099_CR41","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/s41431-018-0107-5","volume":"26","author":"C Tunca","year":"2018","unstructured":"Tunca C, Akcimen F, Coskun C, Gundogdu-Eken A, Kocoglu C, Cevik B, et al. ERLIN1 mutations cause teenage-onset slowly progressive ALS in a large Turkish pedigree. Eur J Hum Genet. 2018;26(5):745\u20138. https:\/\/doi.org\/10.1038\/s41431-018-0107-5.","journal-title":"Eur J Hum Genet"},{"issue":"6","key":"1099_CR42","doi-asserted-by":"publisher","first-page":"e374","DOI":"10.1212\/NXG.0000000000000374","volume":"5","author":"MD Amador","year":"2019","unstructured":"Amador MD, Muratet F, Teyssou E, Banneau G, Danel-Brunaud V, Allart E, et al. Spastic paraplegia due to recessive or dominant mutations in ERLIN2 can convert to ALS. Neurol Genet. 2019;5(6):e374. https:\/\/doi.org\/10.1212\/NXG.0000000000000374.","journal-title":"Neurol Genet"},{"issue":"4","key":"1099_CR43","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1002\/ana.23641","volume":"72","author":"A Al-Saif","year":"2012","unstructured":"Al-Saif A, Bohlega S, Al-Mohanna F. Loss of ERLIN2 function leads to juvenile primary lateral sclerosis. Ann Neurol. 2012;72(4):510\u20136. https:\/\/doi.org\/10.1002\/ana.23641.","journal-title":"Ann Neurol"},{"issue":"1","key":"1099_CR44","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.bbrc.2011.10.032","volume":"415","author":"D Pednekar","year":"2011","unstructured":"Pednekar D, Wang Y, Fedotova TV, Wojcikiewicz RJ. Clustered hydrophobic amino acids in amphipathic helices mediate erlin1\/2 complex assembly. Biochem Biophys Res Commun. 2011;415(1):135\u201340. https:\/\/doi.org\/10.1016\/j.bbrc.2011.10.032.","journal-title":"Biochem Biophys Res Commun"},{"issue":"4","key":"1099_CR45","doi-asserted-by":"publisher","first-page":"839 e5","DOI":"10.1016\/j.neurobiolaging.2011.11.012","volume":"33","author":"H Daoud","year":"2012","unstructured":"Daoud H, Zhou S, Noreau A, Sabbagh M, Belzil V, Dionne-Laporte A, et al. Exome sequencing reveals SPG11 mutations causing juvenile ALS. Neurobiol Aging. 2012;33(4):839 e5\u20139. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2011.11.012.","journal-title":"Neurobiol Aging"},{"issue":"10","key":"1099_CR46","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1002\/mds.27491","volume":"33","author":"I Faber","year":"2018","unstructured":"Faber I, Martinez ARM, Martins CR Jr, Maia ML, Souza JP, Lourenco CM, et al. SPG11-related parkinsonism: clinical profile, molecular imaging and l-dopa response. Mov Disord. 2018;33(10):1650\u20136. https:\/\/doi.org\/10.1002\/mds.27491.","journal-title":"Mov Disord"},{"issue":"2","key":"1099_CR47","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1093\/brain\/aww307","volume":"140","author":"A Estrada-Cuzcano","year":"2017","unstructured":"Estrada-Cuzcano A, Martin S, Chamova T, Synofzik M, Timmann D, Holemans T, et al. Loss-of-function mutations in the ATP13A2\/PARK9 gene cause complicated hereditary spastic paraplegia (SPG78). Brain. 2017;140(2):287\u2013305. https:\/\/doi.org\/10.1093\/brain\/aww307.","journal-title":"Brain."},{"issue":"10","key":"1099_CR48","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1038\/ng1884","volume":"38","author":"A Ramirez","year":"2006","unstructured":"Ramirez A, Heimbach A, Grundemann J, Stiller B, Hampshire D, Cid LP, et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet. 2006;38(10):1184\u201391. https:\/\/doi.org\/10.1038\/ng1884.","journal-title":"Nat Genet"},{"issue":"6701","key":"1099_CR49","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/26652","volume":"395","author":"E Leroy","year":"1998","unstructured":"Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, et al. The ubiquitin pathway in Parkinson\u2019s disease. Nature. 1998;395(6701):451\u20132. https:\/\/doi.org\/10.1038\/26652.","journal-title":"Nature."},{"issue":"9","key":"1099_CR50","doi-asserted-by":"publisher","first-page":"3489","DOI":"10.1073\/pnas.1222732110","volume":"110","author":"K Bilguvar","year":"2013","unstructured":"Bilguvar K, Tyagi NK, Ozkara C, Tuysuz B, Bakircioglu M, Choi M, et al. Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration. Proc Natl Acad Sci U S A. 2013;110(9):3489\u201394. https:\/\/doi.org\/10.1073\/pnas.1222732110.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"16","key":"1099_CR51","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1093\/hmg\/ddg211","volume":"12","author":"H Osaka","year":"2003","unstructured":"Osaka H, Wang YL, Takada K, Takizawa S, Setsuie R, Li H, et al. Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron. Hum Mol Genet. 2003;12(16):1945\u201358. https:\/\/doi.org\/10.1093\/hmg\/ddg211.","journal-title":"Hum Mol Genet"},{"issue":"6","key":"1099_CR52","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1001\/jamaneurol.2013.1174","volume":"70","author":"B Arif","year":"2013","unstructured":"Arif B, Kumar KR, Seibler P, Vulinovic F, Fatima A, Winkler S, et al. A novel OPA3 mutation revealed by exome sequencing: an example of reverse phenotyping. JAMA Neurol. 2013;70(6):783\u20137. https:\/\/doi.org\/10.1001\/jamaneurol.2013.1174.","journal-title":"JAMA Neurol"},{"key":"1099_CR53","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.ymgmr.2018.07.003","volume":"16","author":"KR Kumar","year":"2018","unstructured":"Kumar KR, Wali G, Davis RL, Mallawaarachchi AC, Palmer EE, Gayevskiy V, et al. Expanding the spectrum of PEX16 mutations and novel insights into disease mechanisms. Mol Genet Metab Rep. 2018;16:46\u201351. https:\/\/doi.org\/10.1016\/j.ymgmr.2018.07.003.","journal-title":"Mol Genet Metab Rep"},{"issue":"4","key":"1099_CR54","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/s10048-016-0495-z","volume":"17","author":"KR Kumar","year":"2016","unstructured":"Kumar KR, Wali GM, Kamate M, Wali G, Minoche AE, Puttick C, et al. Defining the genetic basis of early onset hereditary spastic paraplegia using whole genome sequencing. Neurogenetics. 2016;17(4):265\u201370. https:\/\/doi.org\/10.1007\/s10048-016-0495-z.","journal-title":"Neurogenetics."},{"issue":"4","key":"1099_CR55","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1002\/ana.23829","volume":"73","author":"K Lohmann","year":"2013","unstructured":"Lohmann K, Wilcox RA, Winkler S, Ramirez A, Rakovic A, Park JS, et al. Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene. Ann Neurol. 2013;73(4):537\u201345. https:\/\/doi.org\/10.1002\/ana.23829.","journal-title":"Ann Neurol"},{"issue":"6","key":"1099_CR56","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1002\/mds.26196","volume":"30","author":"D Kancheva","year":"2015","unstructured":"Kancheva D, Chamova T, Guergueltcheva V, Mitev V, Azmanov DN, Kalaydjieva L, et al. Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia. Mov Disord. 2015;30(6):854\u20138. https:\/\/doi.org\/10.1002\/mds.26196.","journal-title":"Mov Disord"},{"issue":"12","key":"1099_CR57","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1016\/S1474-4422(19)30235-2","volume":"18","author":"S Shribman","year":"2019","unstructured":"Shribman S, Reid E, Crosby AH, Houlden H, Warner TT. Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches. Lancet Neurol. 2019;18(12):1136\u201346. https:\/\/doi.org\/10.1016\/S1474-4422(19)30235-2.","journal-title":"Lancet Neurol"},{"issue":"3","key":"1099_CR58","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1007\/s00415-014-7265-3","volume":"261","author":"Z Fan","year":"2014","unstructured":"Fan Z, Greenwood R, Felix AC, Shiloh-Malawsky Y, Tennison M, Roche M, et al. GCH1 heterozygous mutation identified by whole-exome sequencing as a treatable condition in a patient presenting with progressive spastic paraplegia. J Neurol. 2014;261(3):622\u20134. https:\/\/doi.org\/10.1007\/s00415-014-7265-3.","journal-title":"J Neurol"},{"issue":"10","key":"1099_CR59","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1007\/s00415-019-09432-8","volume":"266","author":"Y Wei","year":"2019","unstructured":"Wei Y, Zhou Y, Yuan J, Ni J, Qian M, Cui L, et al. Treatable cause of hereditary spastic paraplegia: eight cases of combined homocysteinaemia with methylmalonic aciduria. J Neurol. 2019;266(10):2434\u20139. https:\/\/doi.org\/10.1007\/s00415-019-09432-8.","journal-title":"J Neurol"},{"issue":"7","key":"1099_CR60","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1001\/jamaneurol.2014.116","volume":"71","author":"A Lossos","year":"2014","unstructured":"Lossos A, Teltsh O, Milman T, Meiner V, Rozen R, Leclerc D, et al. Severe methylenetetrahydrofolate reductase deficiency: clinical clues to a potentially treatable cause of adult-onset hereditary spastic paraplegia. JAMA Neurol. 2014;71(7):901\u20134. https:\/\/doi.org\/10.1001\/jamaneurol.2014.116.","journal-title":"JAMA Neurol"},{"issue":"4","key":"1099_CR61","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1136\/practneurol-2015-001117","volume":"15","author":"Z Nicholls","year":"2015","unstructured":"Nicholls Z, Hobson E, Martindale J, Shaw PJ. Diagnosis of spinal xanthomatosis by next-generation sequencing: identifying a rare, treatable mimic of hereditary spastic paraparesis. Pract Neurol. 2015;15(4):280\u20133. https:\/\/doi.org\/10.1136\/practneurol-2015-001117.","journal-title":"Pract Neurol"},{"key":"1099_CR62","unstructured":"Raymond GV, Moser AB, Fatemi A. X-linked adrenoleukodystrophy. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al., editors. GeneReviews((R)). Seattle (WA)1993."},{"issue":"4","key":"1099_CR63","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.pediatrneurol.2012.06.012","volume":"47","author":"JP Tsang","year":"2012","unstructured":"Tsang JP, Poon WL, Luk HM, Fung CW, Ching CK, Mak CM, et al. Arginase deficiency with new phenotype and a novel mutation: contemporary summary. Pediatr Neurol. 2012;47(4):263\u20139. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2012.06.012.","journal-title":"Pediatr Neurol"},{"issue":"3","key":"1099_CR64","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.ymgme.2015.08.012","volume":"116","author":"B Wolf","year":"2015","unstructured":"Wolf B. Biotinidase deficiency should be considered in individuals exhibiting myelopathy with or without and vision loss. Mol Genet Metab. 2015;116(3):113\u20138. https:\/\/doi.org\/10.1016\/j.ymgme.2015.08.012.","journal-title":"Mol Genet Metab"},{"key":"1099_CR65","unstructured":"Wolf B. Biotinidase deficiency. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al., editors. GeneReviews((R)). Seattle (WA)1993."},{"issue":"10","key":"1099_CR66","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1111\/jcmm.13154","volume":"21","author":"Y Wang","year":"2017","unstructured":"Wang Y, Smith C, Parboosingh JS, Khan A, Innes M, Hekimi S. Pathogenicity of two COQ7 mutations and responses to 2,4-dihydroxybenzoate bypass treatment. J Cell Mol Med. 2017;21(10):2329\u201343. https:\/\/doi.org\/10.1111\/jcmm.13154.","journal-title":"J Cell Mol Med"},{"key":"1099_CR67","unstructured":"Salviati L, Trevisson E, Doimo M, Navas P. Primary coenzyme Q10 deficiency. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al., editors. GeneReviews((R)). Seattle (WA)1993."},{"issue":"Pt 5","key":"1099_CR68","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1093\/brain\/123.5.908","volume":"123","author":"A Verrips","year":"2000","unstructured":"Verrips A, Hoefsloot LH, Steenbergen GC, Theelen JP, Wevers RA, Gabreels FJ, et al. Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis. Brain. 2000;123(Pt 5):908\u201319. https:\/\/doi.org\/10.1093\/brain\/123.5.908.","journal-title":"Brain."},{"issue":"6","key":"1099_CR69","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1136\/jnnp.71.6.795","volume":"71","author":"S Kasim","year":"2001","unstructured":"Kasim S, Moo LR, Zschocke J, Jinnah HA. Phenylketonuria presenting in adulthood as progressive spastic paraparesis with dementia. J Neurol Neurosurg Psychiatry. 2001;71(6):795\u20137. https:\/\/doi.org\/10.1136\/jnnp.71.6.795.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"2","key":"1099_CR70","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.ejpn.2019.02.010","volume":"23","author":"A Verrotti","year":"2019","unstructured":"Verrotti A, Di Francesco L, Striano P. GLUT1 deficiency and pediatric-onset hereditary spastic paraplegia: a new association. Eur J Paediatr Neurol. 2019;23(2):233\u20134. https:\/\/doi.org\/10.1016\/j.ejpn.2019.02.010.","journal-title":"Eur J Paediatr Neurol"},{"issue":"1","key":"1099_CR71","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1002\/ana.24671","volume":"80","author":"JF Vazquez-Costa","year":"2016","unstructured":"Vazquez-Costa JF, Bataller L, Vilchez JJ. Primary lateral sclerosis and hereditary spastic paraplegia in sporadic patients. An important distinction in descriptive studies. Ann Neurol. 2016;80(1):169\u201370. https:\/\/doi.org\/10.1002\/ana.24671.","journal-title":"Ann Neurol"},{"issue":"5","key":"1099_CR72","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1111\/ene.12669","volume":"22","author":"N Geevasinga","year":"2015","unstructured":"Geevasinga N, Menon P, Sue CM, Kumar KR, Ng K, Yiannikas C, et al. Cortical excitability changes distinguish the motor neuron disease phenotypes from hereditary spastic paraplegia. Eur J Neurol. 2015;22(5):826\u201331, e57-8. https:\/\/doi.org\/10.1111\/ene.12669.","journal-title":"Eur J Neurol"},{"issue":"4","key":"1099_CR73","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1001\/archneurol.2009.19","volume":"66","author":"F Brugman","year":"2009","unstructured":"Brugman F, Veldink JH, Franssen H, de Visser M, de Jong JM, Faber CG, et al. Differentiation of hereditary spastic paraparesis from primary lateral sclerosis in sporadic adult-onset upper motor neuron syndromes. Arch Neurol. 2009;66(4):509\u201314. https:\/\/doi.org\/10.1001\/archneurol.2009.19.","journal-title":"Arch Neurol"},{"issue":"5","key":"1099_CR74","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1002\/mds.27655","volume":"34","author":"TS Pearson","year":"2019","unstructured":"Pearson TS, Pons R, Ghaoui R, Sue CM. Genetic mimics of cerebral palsy. Mov Disord. 2019;34(5):625\u201336. https:\/\/doi.org\/10.1002\/mds.27655.","journal-title":"Mov Disord"},{"issue":"3","key":"1099_CR75","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1001\/archneur.63.3.445","volume":"63","author":"S Rainier","year":"2006","unstructured":"Rainier S, Sher C, Reish O, Thomas D, Fink JK. De novo occurrence of novel SPG3A\/atlastin mutation presenting as cerebral palsy. Arch Neurol. 2006;63(3):445\u20137. https:\/\/doi.org\/10.1001\/archneur.63.3.445.","journal-title":"Arch Neurol"},{"key":"1099_CR76","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.jns.2017.01.069","volume":"375","author":"A Rubegni","year":"2017","unstructured":"Rubegni A, Battisti C, Tessa A, Cerase A, Doccini S, Malandrini A, et al. SPG2 mimicking multiple sclerosis in a family identified using next generation sequencing. J Neurol Sci. 2017;375:198\u2013202. https:\/\/doi.org\/10.1016\/j.jns.2017.01.069.","journal-title":"J Neurol Sci"},{"issue":"1","key":"1099_CR77","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1002\/ana.25263","volume":"84","author":"X Jia","year":"2018","unstructured":"Jia X, Madireddy L, Caillier S, Santaniello A, Esposito F, Comi G, et al. Genome sequencing uncovers phenocopies in primary progressive multiple sclerosis. Ann Neurol. 2018;84(1):51\u201363. https:\/\/doi.org\/10.1002\/ana.25263.","journal-title":"Ann Neurol"},{"issue":"3","key":"1099_CR78","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s00401-013-1115-8","volume":"126","author":"JK Fink","year":"2013","unstructured":"Fink JK. Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms. Acta Neuropathol. 2013;126(3):307\u201328. https:\/\/doi.org\/10.1007\/s00401-013-1115-8.","journal-title":"Acta Neuropathol"},{"issue":"12","key":"1099_CR79","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1093\/hmg\/dds089","volume":"21","author":"J Bras","year":"2012","unstructured":"Bras J, Verloes A, Schneider SA, Mole SE, Guerreiro RJ. Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-lipofuscinosis. Hum Mol Genet. 2012;21(12):2646\u201350. https:\/\/doi.org\/10.1093\/hmg\/dds089.","journal-title":"Hum Mol Genet"},{"issue":"8","key":"1099_CR80","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1002\/mds.22947","volume":"25","author":"SA Schneider","year":"2010","unstructured":"Schneider SA, Paisan-Ruiz C, Quinn NP, Lees AJ, Houlden H, Hardy J, et al. ATP13A2 mutations (PARK9) cause neurodegeneration with brain iron accumulation. Mov Disord. 2010;25(8):979\u201384. https:\/\/doi.org\/10.1002\/mds.22947.","journal-title":"Mov Disord"},{"issue":"12","key":"1099_CR81","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx280","volume":"140","author":"S de Bot","year":"2017","unstructured":"de Bot S, Kamsteeg EJ, Van De Warrenburg BPC. Complicated hereditary spastic paraplegia due to ATP13A2 mutations: what\u2019s in a name? Brain. 2017;140(12):e73. https:\/\/doi.org\/10.1093\/brain\/awx280.","journal-title":"Brain."},{"issue":"6","key":"1099_CR82","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1093\/brain\/awx095","volume":"140","author":"M Minnerop","year":"2017","unstructured":"Minnerop M, Kurzwelly D, Wagner H, Soehn AS, Reichbauer J, Tao F, et al. Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia. Brain. 2017;140(6):1561\u201378. https:\/\/doi.org\/10.1093\/brain\/awx095.","journal-title":"Brain."},{"issue":"1","key":"1099_CR83","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/brain\/awx290","volume":"141","author":"L Gauquelin","year":"2018","unstructured":"Gauquelin L, Tetreault M, Thiffault I, Farrow E, Miller N, Yoo B, et al. POLR3A variants in hereditary spastic paraplegia and ataxia. Brain. 2018;141(1):e1. https:\/\/doi.org\/10.1093\/brain\/awx290.","journal-title":"Brain."},{"issue":"6","key":"1099_CR84","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/ejhg.2011.261","volume":"20","author":"S Klebe","year":"2012","unstructured":"Klebe S, Lossos A, Azzedine H, Mundwiller E, Sheffer R, Gaussen M, et al. KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations. Eur J Hum Genet. 2012;20(6):645\u20139. https:\/\/doi.org\/10.1038\/ejhg.2011.261.","journal-title":"Eur J Hum Genet"},{"issue":"1","key":"1099_CR85","doi-asserted-by":"publisher","first-page":"12527","DOI":"10.1038\/s41598-017-12999-9","volume":"7","author":"CK Cheon","year":"2017","unstructured":"Cheon CK, Lim SH, Kim YM, Kim D, Lee NY, Yoon TS, et al. Autosomal dominant transmission of complicated hereditary spastic paraplegia due to a dominant negative mutation of KIF1A, SPG30 gene. Sci Rep. 2017;7(1):12527. https:\/\/doi.org\/10.1038\/s41598-017-12999-9.","journal-title":"Sci Rep"},{"issue":"12","key":"1099_CR86","doi-asserted-by":"publisher","first-page":"2684","DOI":"10.1007\/s00415-015-7899-9","volume":"262","author":"A Citterio","year":"2015","unstructured":"Citterio A, Arnoldi A, Panzeri E, Merlini L, D\u2019Angelo MG, Musumeci O, et al. Variants in KIF1A gene in dominant and sporadic forms of hereditary spastic paraparesis. J Neurol. 2015;262(12):2684\u201390. https:\/\/doi.org\/10.1007\/s00415-015-7899-9.","journal-title":"J Neurol"},{"issue":"10","key":"1099_CR87","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1038\/ejhg.2014.297","volume":"23","author":"E Ylikallio","year":"2015","unstructured":"Ylikallio E, Kim D, Isohanni P, Auranen M, Kim E, Lonnqvist T, et al. Dominant transmission of de novo KIF1A motor domain variant underlying pure spastic paraplegia. Eur J Hum Genet. 2015;23(10):1427\u201330. https:\/\/doi.org\/10.1038\/ejhg.2014.297.","journal-title":"Eur J Hum Genet"},{"issue":"12","key":"1099_CR88","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/jhg.2015.108","volume":"60","author":"C Ohba","year":"2015","unstructured":"Ohba C, Haginoya K, Osaka H, Kubota K, Ishiyama A, Hiraide T, et al. De novo KIF1A mutations cause intellectual deficit, cerebellar atrophy, lower limb spasticity and visual disturbance. J Hum Genet. 2015;60(12):739\u201342. https:\/\/doi.org\/10.1038\/jhg.2015.108.","journal-title":"J Hum Genet"},{"issue":"2","key":"1099_CR89","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.ajhg.2013.12.005","volume":"94","author":"T Esteves","year":"2014","unstructured":"Esteves T, Durr A, Mundwiller E, Loureiro JL, Boutry M, Gonzalez MA, et al. Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia. Am J Hum Genet. 2014;94(2):268\u201377. https:\/\/doi.org\/10.1016\/j.ajhg.2013.12.005.","journal-title":"Am J Hum Genet"},{"issue":"10","key":"1099_CR90","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1038\/ejhg.2014.5","volume":"22","author":"TN Khan","year":"2014","unstructured":"Khan TN, Klar J, Tariq M, Anjum Baig S, Malik NA, Yousaf R, et al. Evidence for autosomal recessive inheritance in SPG3A caused by homozygosity for a novel ATL1 missense mutation. Eur J Hum Genet. 2014;22(10):1180\u20134. https:\/\/doi.org\/10.1038\/ejhg.2014.5.","journal-title":"Eur J Hum Genet"},{"issue":"6","key":"1099_CR91","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/jhg.2016.6","volume":"61","author":"L Willkomm","year":"2016","unstructured":"Willkomm L, Heredia R, Hoffmann K, Wang H, Voit T, Hoffman EP, et al. Homozygous mutation in Atlastin GTPase 1 causes recessive hereditary spastic paraplegia. J Hum Genet. 2016;61(6):571\u20133. https:\/\/doi.org\/10.1038\/jhg.2016.6.","journal-title":"J Hum Genet"},{"key":"1099_CR92","doi-asserted-by":"publisher","unstructured":"Aguilera-Albesa S, de la Hoz AB, Ibarluzea N, Ordonez-Castillo AR, Busto-Crespo O, Villate O, et al. Hereditary spastic paraplegia and intellectual disability: clinicogenetic lessons from a family suggesting a dual genetics diagnosis. Front Neurol. 2020;11:\u201341. https:\/\/doi.org\/10.3389\/fneur.2020.00041A recent study showing concurrent genetic diagnoses in a family with HSP.","DOI":"10.3389\/fneur.2020.00041"},{"issue":"1","key":"1099_CR93","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1056\/NEJMoa1516767","volume":"376","author":"JE Posey","year":"2017","unstructured":"Posey JE, Harel T, Liu P, Rosenfeld JA, James RA, Coban Akdemir ZH, et al. Resolution of disease phenotypes resulting from multilocus genomic variation. N Engl J Med. 2017;376(1):21\u201331. https:\/\/doi.org\/10.1056\/NEJMoa1516767.","journal-title":"N Engl J Med"},{"issue":"1","key":"1099_CR94","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1002\/acn3.50967","volume":"7","author":"E Verdura","year":"2020","unstructured":"Verdura E, Schluter A, Fernandez-Eulate G, Ramos-Martin R, Zulaica M, Planas-Serra L, et al. A deep intronic splice variant advises reexamination of presumably dominant SPG7 Cases. Ann Clin Transl Neurol. 2020;7(1):105\u201311. https:\/\/doi.org\/10.1002\/acn3.50967This report highlights the utility of WGS in detecting deep intronic variants in the SPG7 gene.","journal-title":"Ann Clin Transl Neurol"},{"issue":"3","key":"1099_CR95","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1111\/j.1399-0004.2012.01896.x","volume":"83","author":"E Sanchez-Ferrero","year":"2013","unstructured":"Sanchez-Ferrero E, Coto E, Beetz C, Gamez J, Corao AI, Diaz M, et al. SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V. Clin Genet. 2013;83(3):257\u201362. https:\/\/doi.org\/10.1111\/j.1399-0004.2012.01896.x.","journal-title":"Clin Genet"},{"key":"1099_CR96","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1055\/s-0039-1688446","volume":"45","author":"KR Kumar","year":"2019","unstructured":"Kumar KR, Cowley MJ, Davis RL. Next-generation sequencing and emerging technologies. Semin Thromb Hemost. 2019;45:661\u201373. https:\/\/doi.org\/10.1055\/s-0039-1688446.","journal-title":"Semin Thromb Hemost"},{"issue":"3","key":"1099_CR97","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s00439-015-1631-9","volume":"135","author":"J Meienberg","year":"2016","unstructured":"Meienberg J, Bruggmann R, Oexle K, Matyas G. Clinical sequencing: is WGS the better WES? Hum Genet. 2016;135(3):359\u201362. https:\/\/doi.org\/10.1007\/s00439-015-1631-9.","journal-title":"Hum Genet"},{"issue":"5","key":"1099_CR98","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/s41436-018-0295-y","volume":"21","author":"AM Gross","year":"2019","unstructured":"Gross AM, Ajay SS, Rajan V, Brown C, Bluske K, Burns NJ, et al. Copy-number variants in clinical genome sequencing: deployment and interpretation for rare and undiagnosed disease. Genet Med. 2019;21(5):1121\u201330. https:\/\/doi.org\/10.1038\/s41436-018-0295-y.","journal-title":"Genet Med"},{"key":"1099_CR99","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/s41436-018-0082-9","volume":"21","author":"EP Kirk","year":"2018","unstructured":"Kirk EP, Barlow-Stewart K, Selvanathan A, Josephi-Taylor S, Worgan L, Rajagopalan S, et al. Beyond the panel: preconception screening in consanguineous couples using the TruSight One \u201cclinical exome\u201d. Genet Med. 2018;21:608\u201312. https:\/\/doi.org\/10.1038\/s41436-018-0082-9.","journal-title":"Genet Med"},{"issue":"11","key":"1099_CR100","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1212\/01.wnl.0000244413.49258.f5","volume":"67","author":"C Beetz","year":"2006","unstructured":"Beetz C, Nygren AO, Schickel J, Auer-Grumbach M, Burk K, Heide G, et al. High frequency of partial SPAST deletions in autosomal dominant hereditary spastic paraplegia. Neurology. 2006;67(11):1926\u201330. https:\/\/doi.org\/10.1212\/01.wnl.0000244413.49258.f5.","journal-title":"Neurology."},{"issue":"11","key":"1099_CR101","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1101\/gr.225672.117","volume":"27","author":"E Dolzhenko","year":"2017","unstructured":"Dolzhenko E, van Vugt J, Shaw RJ, Bekritsky MA, van Blitterswijk M, Narzisi G, et al. Detection of long repeat expansions from PCR-free whole-genome sequence data. Genome Res. 2017;27(11):1895\u2013903. https:\/\/doi.org\/10.1101\/gr.225672.117.","journal-title":"Genome Res"},{"issue":"5","key":"1099_CR102","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1002\/jimd.12109","volume":"42","author":"M Wagner","year":"2019","unstructured":"Wagner M, Berutti R, Lorenz-Depiereux B, Graf E, Eckstein G, Mayr JA, et al. Mitochondrial DNA mutation analysis from exome sequencing-a more holistic approach in diagnostics of suspected mitochondrial disease. J Inherit Metab Dis. 2019;42(5):909\u201317. https:\/\/doi.org\/10.1002\/jimd.12109.","journal-title":"J Inherit Metab Dis"},{"key":"1099_CR103","doi-asserted-by":"crossref","unstructured":"Puttick C, Kumar KR, Davis RL, Pinese M, Thomas DM, Dinger ME et al. <em>mity<\/em>: a highly sensitive mitochondrial variant analysis pipeline for whole genome sequencing data. bioRxiv. 2019:852210. 10.1101\/852210.","DOI":"10.1101\/852210"},{"issue":"11","key":"1099_CR104","doi-asserted-by":"publisher","first-page":"3026","DOI":"10.1172\/JCI24694","volume":"115","author":"G Orso","year":"2005","unstructured":"Orso G, Martinuzzi A, Rossetto MG, Sartori E, Feany M, Daga A. Disease-related phenotypes in a Drosophila model of hereditary spastic paraplegia are ameliorated by treatment with vinblastine. J Clin Invest. 2005;115(11):3026\u201334. https:\/\/doi.org\/10.1172\/JCI24694.","journal-title":"J Clin Invest"},{"issue":"1","key":"1099_CR105","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1242\/dmm.008946","volume":"6","author":"C Fassier","year":"2013","unstructured":"Fassier C, Tarrade A, Peris L, Courageot S, Mailly P, Dalard C, et al. Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice. Dis Model Mech. 2013;6(1):72\u201383. https:\/\/doi.org\/10.1242\/dmm.008946.","journal-title":"Dis Model Mech"},{"issue":"6","key":"1099_CR106","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1242\/bio.20147641","volume":"3","author":"Y Fan","year":"2014","unstructured":"Fan Y, Wali G, Sutharsan R, Bellette B, Crane DI, Sue CM, et al. Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in hereditary spastic paraplegia. Biol Open. 2014;3(6):494\u2013502. https:\/\/doi.org\/10.1242\/bio.20147641.","journal-title":"Biol Open"},{"issue":"8","key":"1099_CR107","doi-asserted-by":"publisher","first-page":"142","DOI":"10.3390\/brainsci8080142","volume":"8","author":"G Wali","year":"2018","unstructured":"Wali G, Sue CM, Mackay-Sim A. Patient-derived stem cell models in SPAST HSP: disease modelling and drug discovery. Brain Sci. 2018;8(8):142. https:\/\/doi.org\/10.3390\/brainsci8080142.","journal-title":"Brain Sci"},{"issue":"4","key":"1099_CR108","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1093\/brain\/awz382","volume":"143","author":"OJ Rickman","year":"2020","unstructured":"Rickman OJ, Baple EL, Crosby AH. Lipid metabolic pathways converge in motor neuron degenerative diseases. Brain. 2020;143(4):1073\u201387. https:\/\/doi.org\/10.1093\/brain\/awz382.","journal-title":"Brain."},{"issue":"12","key":"1099_CR109","doi-asserted-by":"publisher","first-page":"3112","DOI":"10.1093\/brain\/awx273","volume":"140","author":"L Schols","year":"2017","unstructured":"Schols L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, et al. Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Brain. 2017;140(12):3112\u201327. https:\/\/doi.org\/10.1093\/brain\/awx273One of two clinical trials investigating the use of cholesterol-lowering drugs to treat SPG5. SPG5 may prove to be the most treatable form of HSP and so in the future, it may be particularly important to identify individuals with CYP7B1 mutations.","journal-title":"Brain"},{"issue":"4","key":"1099_CR110","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1194\/jlr.M002543","volume":"51","author":"R Schule","year":"2010","unstructured":"Schule R, Siddique T, Deng HX, Yang Y, Donkervoort S, Hansson M, et al. Marked accumulation of 27-hydroxycholesterol in SPG5 patients with hereditary spastic paresis. J Lipid Res. 2010;51(4):819\u201323. https:\/\/doi.org\/10.1194\/jlr.M002543.","journal-title":"J Lipid Res"},{"issue":"1","key":"1099_CR111","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1093\/brain\/awx297","volume":"141","author":"C Marelli","year":"2018","unstructured":"Marelli C, Lamari F, Rainteau D, Lafourcade A, Banneau G, Humbert L, et al. Plasma oxysterols: biomarkers for diagnosis and treatment in spastic paraplegia type 5. Brain. 2018;141(1):72\u201384. https:\/\/doi.org\/10.1093\/brain\/awx297The other clinical trial investigating the use of cholesterol-lowering drugs to treat SPG5.","journal-title":"Brain"},{"key":"1099_CR112","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.omtm.2019.10.011","volume":"15","author":"S Hauser","year":"2019","unstructured":"Hauser S, Poenisch M, Schelling Y, Hoflinger P, Schuster S, Teegler A, et al. mRNA as a novel treatment strategy for hereditary spastic paraplegia type 5. Mol Ther Methods Clin Dev. 2019;15:359\u201370. https:\/\/doi.org\/10.1016\/j.omtm.2019.10.011.","journal-title":"Mol Ther Methods Clin Dev"},{"issue":"Pt 7","key":"1099_CR113","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1093\/brain\/aww111","volume":"139","author":"E Kara","year":"2016","unstructured":"Kara E, Tucci A, Manzoni C, Lynch DS, Elpidorou M, Bettencourt C, et al. Genetic and phenotypic characterization of complex hereditary spastic paraplegia. Brain. 2016;139(Pt 7):1904\u201318. https:\/\/doi.org\/10.1093\/brain\/aww111.","journal-title":"Brain."},{"issue":"4","key":"1099_CR114","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1002\/ana.24611","volume":"79","author":"R Schule","year":"2016","unstructured":"Schule R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S, et al. Hereditary spastic paraplegia: clinicogenetic lessons from 608 patients. Ann Neurol. 2016;79(4):646\u201358. https:\/\/doi.org\/10.1002\/ana.24611.","journal-title":"Ann Neurol"}],"container-title":["Current Neurology and Neuroscience Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11910-021-01099-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11910-021-01099-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11910-021-01099-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T12:40:35Z","timestamp":1615984835000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11910-021-01099-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,28]]},"references-count":114,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["1099"],"URL":"https:\/\/doi.org\/10.1007\/s11910-021-01099-x","relation":{},"ISSN":["1528-4042","1534-6293"],"issn-type":[{"value":"1528-4042","type":"print"},{"value":"1534-6293","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,28]]},"assertion":[{"value":"21 January 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"Lydia Saputra and Kishore Raj Kumar have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This article does not contain any original studies with human or animal subjects performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights and Informed Consent"}}],"article-number":"15"}}