{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:07:22Z","timestamp":1792199242457,"version":"4.4.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T00:00:00Z","timestamp":1490918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0174667","type":"journal-article","created":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T14:37:55Z","timestamp":1490971075000},"page":"e0174667","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":54,"title":["Targeted high throughput sequencing in hereditary ataxia and spastic paraplegia"],"prefix":"10.1371","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6387-8019","authenticated-orcid":true,"given":"Zafar","family":"Iqbal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siri L.","family":"Rydning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iselin M.","family":"Wedding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Koht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasse","family":"Pihlstr\u00f8m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aina H.","family":"Rengmark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra P.","family":"Henriksen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal M. E.","family":"Tallaksen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Toft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,3,31]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/S0140-6736(83)92879-9","article-title":"Classification of the hereditary ataxias and paraplegias","volume":"1","author":"AE Harding","year":"1983","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1093\/brain\/awp056","article-title":"Prevalence of hereditary ataxia and spastic paraplegia in southeast Norway: a population-based study","volume":"132","author":"AK Erichsen","year":"2009","journal-title":"Brain"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/978-90-481-2813-6_18","article-title":"Genetics and pathogenesis of inherited ataxias and spastic paraplegias","volume":"652","author":"C Espinos","year":"2009","journal-title":"Adv Exp Med Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.expneurol.2014.06.011","article-title":"Hereditary spastic paraplegia: clinical-genetic characteristics and evolving molecular mechanisms","volume":"261","author":"T Lo Giudice","year":"2014","journal-title":"Exp Neurol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1055\/s-0034-1386766","article-title":"Genetic cerebellar ataxias","volume":"34","author":"E Storey","year":"2014","journal-title":"Semin Neurol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1007\/s00415-014-7598-y","article-title":"Diagnosis, investigation and management of hereditary spastic paraplegias in the era of next-generation sequencing","volume":"262","author":"A Hensiek","year":"2015","journal-title":"J Neurol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"586","DOI":"10.3390\/genes5030586","article-title":"Genes and genetic testing in hereditary ataxias","volume":"5","author":"E Sandford","year":"2014","journal-title":"Genes (Basel)"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jmoldx.2015.10.005","article-title":"Assessment of Targeted Next-Generation Sequencing as a Tool for the Diagnosis of Charcot-Marie-Tooth Disease and Hereditary Motor Neuropathy","volume":"18","author":"V Lupo","year":"2016","journal-title":"J Mol Diagn"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1600 e1605","DOI":"10.1016\/j.neurobiolaging.2014.12.017","article-title":"Investigation of next-generation sequencing technologies as a diagnostic tool for amyotrophic lateral sclerosis","volume":"36","author":"S Morgan","year":"2015","journal-title":"Neurobiol Aging"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"e53083","DOI":"10.1371\/journal.pone.0053083","article-title":"Comprehensive mutation analysis for congenital muscular dystrophy: a clinical PCR-based enrichment and next-generation sequencing panel","volume":"8","author":"CA Valencia","year":"2013","journal-title":"PLoS One"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1055\/s-0034-1386767","article-title":"Hereditary spastic paraplegia: clinical principles and genetic advances","volume":"34","author":"JK Fink","year":"2014","journal-title":"Semin Neurol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1212\/WNL.46.6.1507","article-title":"Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working group","volume":"46","author":"JK Fink","year":"1996","journal-title":"Neurology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/ahg.12060","article-title":"Effective variant detection by targeted deep sequencing of DNA pools: an example from Parkinson's disease","volume":"78","author":"L Pihlstrom","year":"2014","journal-title":"Ann Hum Genet"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"M Kircher","year":"2014","journal-title":"Nat Genet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1101\/gr.183483.114","article-title":"Actionable exomic incidental findings in 6503 participants: challenges of variant classification","volume":"25","author":"LM Amendola","year":"2015","journal-title":"Genome Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/humu.20682","article-title":"A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia","volume":"29","author":"A Arnoldi","year":"2008","journal-title":"Hum Mutat"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/j.1468-1331.2007.01861.x","article-title":"Seven novel mutations and four exon deletions in a collection of Norwegian patients with SPG4 hereditary spastic paraplegia","volume":"14","author":"AK Erichsen","year":"2007","journal-title":"Eur J Neurol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"E376","DOI":"10.1002\/humu.20920","article-title":"Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10","volume":"30","author":"C Goizet","year":"2009","journal-title":"Hum Mutat"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1002\/ana.23701","article-title":"Mutations in KCND3 cause spinocerebellar ataxia type 22","volume":"72","author":"YC Lee","year":"2012","journal-title":"Ann Neurol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1399-0004.2012.01896.x","article-title":"SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V","volume":"83","author":"E Sanchez-Ferrero","year":"2013","journal-title":"Clin Genet"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"e86340","DOI":"10.1371\/journal.pone.0086340","article-title":"Spastic paraplegia type 7 is associated with multiple mitochondrial DNA deletions","volume":"9","author":"IM Wedding","year":"2014","journal-title":"PLoS One"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/ng1313","article-title":"Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome","volume":"36","author":"C Windpassinger","year":"2004","journal-title":"Nat Genet"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1111\/ene.12937","article-title":"A founder mutation p.H701P identified as a major cause of SPG7 in Norway","volume":"23","author":"SL Rydning","year":"2016","journal-title":"Eur J Neurol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nature11405","article-title":"An anatomically comprehensive atlas of the adult human brain transcriptome","volume":"489","author":"MJ Hawrylycz","year":"2012","journal-title":"Nature"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/S1474-4422(10)70183-6","article-title":"Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond","volume":"9","author":"A Durr","year":"2010","journal-title":"Lancet Neurol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nrneurol.2009.26","article-title":"Diagnosis and treatment of Friedreich ataxia: a European perspective","volume":"5","author":"JB Schulz","year":"2009","journal-title":"Nat Rev Neurol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1468-1331.2009.02873.x","article-title":"EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias","volume":"17","author":"T Gasser","year":"2010","journal-title":"Eur J Neurol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1001\/jama.2014.1717","article-title":"Clinical interpretation and implications of whole-genome sequencing","volume":"311","author":"FE Dewey","year":"2014","journal-title":"JAMA"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/ejhg.2011.258","article-title":"Disease gene identification strategies for exome sequencing","volume":"20","author":"C Gilissen","year":"2012","journal-title":"Eur J Hum Genet"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrg3999","article-title":"Genetic studies in intellectual disability and related disorders","volume":"17","author":"LE Vissers","year":"2016","journal-title":"Nat Rev Genet"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1002\/humu.22450","article-title":"A post-hoc comparison of the utility of sanger sequencing and exome sequencing for the diagnosis of heterogeneous diseases","volume":"34","author":"K Neveling","year":"2013","journal-title":"Hum Mutat"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1136\/jmedgenet-2015-103144","article-title":"The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists","volume":"52","author":"K Boycott","year":"2015","journal-title":"J Med Genet"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1093\/brain\/awt236","article-title":"Next generation sequencing for molecular diagnosis of neurological disorders using ataxias as a model","volume":"136","author":"AH Nemeth","year":"2013","journal-title":"Brain"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1007\/s00415-013-7008-x","article-title":"Targeted next generation sequencing in SPAST-negative hereditary spastic paraplegia","volume":"260","author":"KR Kumar","year":"2013","journal-title":"J Neurol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1001\/jamaneurol.2014.1944","article-title":"Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia","volume":"71","author":"BL Fogel","year":"2014","journal-title":"JAMA Neurol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/brain\/awu348","article-title":"Exome sequencing in undiagnosed inherited and sporadic ataxias","volume":"138","author":"A Pyle","year":"2015","journal-title":"Brain"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1093\/brain\/aww111","article-title":"Genetic and phenotypic characterization of complex hereditary spastic paraplegia","volume":"139","author":"E Kara","year":"2016","journal-title":"Brain"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1038\/ejhg.2016.42","article-title":"Clinical exome sequencing for cerebellar ataxia and spastic paraplegia uncovers novel gene-disease associations and unanticipated rare disorders","volume":"24","author":"BP van de Warrenburg","year":"2016","journal-title":"Eur J Hum Genet"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s10048-013-0375-8","article-title":"Diagnostic utility of whole exome sequencing in patients showing cerebellar and\/or vermis atrophy in childhood","volume":"14","author":"C Ohba","year":"2013","journal-title":"Neurogenetics"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/humu.22451","article-title":"Exome sequencing as a diagnostic tool for pediatric-onset ataxia","volume":"35","author":"SL Sawyer","year":"2014","journal-title":"Hum Mutat"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1101\/gr.117143.110","article-title":"Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis","volume":"21","author":"Y Erlich","year":"2011","journal-title":"Genome Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/ejhg.2015.217","article-title":"De novo dominant variants affecting the motor domain of KIF1A are a cause of PEHO syndrome","volume":"24","author":"S Langlois","year":"2016","journal-title":"Eur J Hum Genet"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1038\/ejhg.2014.297","article-title":"Dominant transmission of de novo KIF1A motor domain variant underlying pure spastic paraplegia","volume":"23","author":"E Ylikallio","year":"2015","journal-title":"Eur J Hum Genet"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/ana.24509","article-title":"New practical definitions for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay","volume":"78","author":"J Pilliod","year":"2015","journal-title":"Ann Neurol"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0186571","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T00:00:00Z","timestamp":1507766400000}}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0174667","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T09:32:52Z","timestamp":1568971972000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0174667"}},"subtitle":[],"editor":[{"given":"Klaus","family":"Brusgaard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,3,31]]},"references-count":45,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,3,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0174667","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pone.0186571","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,31]]}}}