{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T10:43:07Z","timestamp":1764499387858},"reference-count":31,"publisher":"Georg Thieme Verlag KG","issue":"05","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background\u2003Recent research suggested an hippocalcin (HPCA)-related form of DYT2-like autosomal recessive dystonia. Two reports highlight a broad spectrum of the clinical phenotype. Here, we describe a novel HPCA gene variant in a pediatric patient and two affected relatives.<\/jats:p><jats:p>\n          Methods\u2003Whole exome sequencing was applied after a thorough clinical and neurological examination of the index patient and her family members. Results of neuropsychological testing were analyzed.<\/jats:p><jats:p>\n          Results\u2003Whole exome sequencing revealed a novel homozygous missense variant in the HPCA gene [c.182C&gt;T p.(Ala61Val)] in our pediatric patient and the two affected family members. Clinically, the cases presented with dystonia, dysarthria, and jerky movements. We observed a particular cognitive profile with executive dysfunctions in our patient, which corresponds to the cognitive deficits that have been observed in the patients previously described.<\/jats:p><jats:p>\n          Conclusion\u2003We present a novel genetic variant of the HPCA gene associated with autosomal recessive dystonia in a child with childhood-onset dystonia supporting its clinical features. Furthermore, we propose specific HPCA-related cognitive changes in homozygous carriers, underlining the importance of undertaking a systematic assessment of cognition in HPCA-related dystonia.<\/jats:p>","DOI":"10.1055\/s-0040-1722686","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T06:26:46Z","timestamp":1611901606000},"page":"377-382","source":"Crossref","is-referenced-by-count":9,"title":["Specific Cognitive Changes due to Hippocalcin Alterations? A Novel Familial Homozygous Hippocalcin Variant Associated with Inherited Dystonia and Altered Cognition"],"prefix":"10.1055","volume":"52","author":[{"given":"Sandy","family":"Siegert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang M.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Neuromuscular Research Department, Medical University of Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Pletschko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reginald E.","family":"Bittner","sequence":"additional","affiliation":[{"name":"Neuromuscular Research Department, Medical University of Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Gobara","sequence":"additional","affiliation":[{"name":"Ambulatorium Sonnenschein, Sozialp\u00e4diatrisches Zentrum, St. P\u00f6lten, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Freilinger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"issue":"07","key":"ref1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/mds.25475","article-title":"Phenomenology and classification of dystonia: a consensus update","volume":"28","author":"A Albanese","year":"2013","journal-title":"Mov Disord"},{"key":"ref2","first-page":"1993","volume-title":"Hereditary Dystonia Overview","author":"C Klein","year":"2003"},{"issue":"04","key":"ref3","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.ajhg.2015.02.007","article-title":"Mutations in HPCA cause autosomal-recessive primary isolated dystonia","volume":"96","author":"G Charlesworth","year":"2015","journal-title":"Am J Hum Genet"},{"issue":"14","key":"ref4","doi-asserted-by":"crossref","first-page":"3597","DOI":"10.1093\/emboj\/19.14.3597","article-title":"NAIP interacts with hippocalcin and protects neurons against calcium-induced cell death through caspase-3-dependent and -independent pathways","volume":"19","author":"E A Mercer","year":"2000","journal-title":"EMBO J"},{"issue":"02","key":"ref5","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0306-4522(00)00201-3","article-title":"Expression of the neuronal calcium sensor protein family in the rat brain","volume":"99","author":"M Paterlini","year":"2000","journal-title":"Neuroscience"},{"issue":"04","key":"ref6","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.tins.2004.01.010","article-title":"Neuronal Ca2+-sensor proteins: multitalented regulators of neuronal function","volume":"27","author":"R D Burgoyne","year":"2004","journal-title":"Trends Neurosci"},{"issue":"03","key":"ref7","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nrn2093","article-title":"Neuronal calcium sensor proteins: generating diversity in neuronal Ca2+ signalling","volume":"8","author":"R D Burgoyne","year":"2007","journal-title":"Nat Rev Neurosci"},{"issue":"13","key":"ref8","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1093\/hmg\/ddx133","article-title":"Biophysical and functional characterization of hippocalcin mutants responsible for human dystonia","volume":"26","author":"N Helassa","year":"2017","journal-title":"Hum Mol Genet"},{"issue":"04","key":"ref9","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.neuron.2005.06.014","article-title":"Hippocalcin functions as a calcium sensor in hippocampal LTD","volume":"47","author":"C L Palmer","year":"2005","journal-title":"Neuron"},{"issue":"08","key":"ref10","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1002\/mds.27442","article-title":"HPCA confirmed as a genetic cause of DYT2-like dystonia phenotype","volume":"33","author":"B Atasu","year":"2018","journal-title":"Mov Disord"},{"issue":"04","key":"ref11","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/mds.27638","article-title":"Delineating the phenotype of autosomal-recessive HPCA mutations: not only isolated dystonia!","volume":"34","author":"B Balint","year":"2019","journal-title":"Mov Disord"},{"issue":"02","key":"ref12","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.neuroscience.2005.02.034","article-title":"Hippocalcin-deficient mice display a defect in cAMP response element-binding protein activation associated with impaired spatial and associative memory","volume":"133","author":"M Kobayashi","year":"2005","journal-title":"Neuroscience"},{"key":"ref13","volume-title":"Wechsler Adult Intelligence Scale","author":"F Petermann","year":"2012","edition":"4th edition."},{"key":"ref14","volume-title":"Vienna Test System: Psychological Assessment","author":"G Schuhfried","year":"2013"},{"key":"ref15","volume-title":"The Wisconsin Card Sorting Test - 64 Card Version","author":"S K Kongs","year":"2000"},{"key":"ref16","volume-title":"Regensburger Wortfl\u00fcssigkeits-Test (RWT)","author":"S Aschenbrenner","year":"2000"},{"key":"ref17","volume-title":"TAP 2.3.1. Testbatterie zur Aufmerksamkeits-pr\u00fcfung Version 2.3.1","author":"P Zimmermann","year":"2017"},{"key":"ref18","volume-title":"Verbaler Lern- und Merkf\u00e4higkeitstest: VLMT, Manual","author":"C Helmstaedter","year":"2001"},{"key":"ref19","volume-title":"Depressions-Inventar f\u00fcr Kinder und Jugendliche (DIKJ). Handanweisung (2., \u00fcberarb. u. neunorm. Aufl.)","author":"J Stiensmeier-Pelster","year":"2000"},{"key":"ref20","volume-title":"DISYPS-III: Diagnostik-System f\u00fcr psychische St\u00f6rungen im Kindes- und Jugendalter nach ICD-10 und DSM 5 [DISYPS-III: Diagnostic system for psychiatric disorders in children and adolescents]","author":"M D\u00f6pfner","year":"2017"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/9781119563600","volume-title":"Research Design and Analysis: A Primer for the Non-Statistician","author":"L Rosenstein","year":"2019"},{"issue":"04","key":"ref22","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: mutation prediction for the deep-sequencing age","volume":"11","author":"J M Schwarz","year":"2014","journal-title":"Nat Methods"},{"issue":"03","key":"ref23","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"},{"issue":"11","key":"ref24","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1093\/cercor\/bhp023","article-title":"Structural correlates of semantic and phonemic fluency ability in first and second languages","volume":"19","author":"A Grogan","year":"2009","journal-title":"Cereb Cortex"},{"issue":"06","key":"ref25","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1002\/hipo.20985","article-title":"The nature and time-course of medial temporal lobe contributions to semantic retrieval: an fMRI study on verbal fluency","volume":"22","author":"S Sheldon","year":"2012","journal-title":"Hippocampus"},{"issue":"04","key":"ref26","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1162\/jocn.2009.21056","article-title":"Task-dependent modulations of prefrontal and hippocampal activity during intrinsic word production","volume":"21","author":"C Whitney","year":"2009","journal-title":"J Cogn Neurosci"},{"issue":"10","key":"ref27","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1002\/mds.27048","article-title":"The cognitive features of idiopathic and DYT1 dystonia","volume":"32","author":"M Jahanshahi","year":"2017","journal-title":"Mov Disord"},{"issue":"03","key":"ref28","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1080\/03610730902922119","article-title":"Extending the administration time of the letter fluency test increases sensitivity to cognitive status in aging","volume":"35","author":"R Holtzer","year":"2009","journal-title":"Exp Aging Res"},{"issue":"07","key":"ref29","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1037\/neu0000286","article-title":"Perseveration during verbal fluency in traumatic brain injury reflects impairments in working memory","volume":"30","author":"S Fischer-Baum","year":"2016","journal-title":"Neuropsychology"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.3389\/fpsyg.2019.01355","article-title":"Executive processes underpin the bilingual advantage on phonemic fluency: evidence from analyses of switching and clustering","volume":"10","author":"J E Marsh","year":"2019","journal-title":"Front Psychol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fnhum.2020.00068","article-title":"Verbal working memory as emergent from language comprehension and production","volume":"14","author":"S C Schwering","year":"2020","journal-title":"Front Hum Neurosci"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0040-1722686.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T22:33:26Z","timestamp":1632177206000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0040-1722686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,28]]},"references-count":31,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2021,9,20]]},"published-print":{"date-parts":[[2021,10]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0040-1722686","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,28]]}}}