{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:34:15Z","timestamp":1791596055436,"version":"4.3.4"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2010,10,15]],"date-time":"2010-10-15T00:00:00Z","timestamp":1287100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100008358","name":"Hersenstichting Nederland","doi-asserted-by":"publisher","award":["KS2009(1)-81"],"award-info":[{"award-number":["KS2009(1)-81"]}],"id":[{"id":"10.13039\/501100008358","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AMC Graduate School, University of Amsterdam"},{"DOI":"10.13039\/100014653","name":"Manchester NIHR Biomedical Research Centre","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pontocerebellar hypoplasia is a group of autosomal recessive neurodegenerative disorders with prenatal onset. The common characteristics are cerebellar hypoplasia with variable atrophy of the cerebellum and the ventral pons. Supratentorial involvement is reflected by variable neocortical atrophy, ventriculomegaly and microcephaly. Mutations in the transfer RNA splicing endonuclease subunit genes (TSEN54, TSEN2, TSEN34) were found to be associated with pontocerebellar hypoplasia types 2 and 4. Mutations in the mitochondrial transfer RNA arginyl synthetase gene (RARS2) were associated with pontocerebellar hypoplasia type 6. We studied a cohort of 169 patients from 141 families for mutations in these genes, of whom 106 patients tested positive for mutations in one of the TSEN genes or the RARS2 gene. In order to delineate the neuroradiological and clinical phenotype of patients with mutations in these genes, we compared this group with 63 patients suspected of pontocerebellar hypoplasia who were negative on mutation analysis. We found a strong correlation (P\u2009&amp;lt;\u20090.0005) between TSEN54 mutations and a dragonfly-like cerebellar pattern on magnetic resonance imaging, in which the cerebellar hemispheres are flat and severely reduced in size and the vermis is relatively spared. Mutations in TSEN54 are clinically associated with dyskinesia and\/or dystonia and variable degrees of spasticity, in some cases with pure generalized spasticity. Nonsense or splice site mutations in TSEN54 are associated with a more severe phenotype of more perinatal symptoms, ventilator dependency and early death. In addition, we present ten new mutations in TSEN54, TSEN2 and RARS2. Furthermore, we show that pontocerebellar hypoplasia type 1 together with elevated cerebrospinal fluid lactate may be caused by RARS2 mutations.<\/jats:p>","DOI":"10.1093\/brain\/awq287","type":"journal-article","created":{"date-parts":[[2010,10,18]],"date-time":"2010-10-18T17:14:58Z","timestamp":1287422098000},"page":"143-156","source":"Crossref","is-referenced-by-count":218,"title":["Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia"],"prefix":"10.1093","volume":"134","author":[{"given":"Yasmin","family":"Namavar","sequence":"first","affiliation":[{"name":"1 Department of Genome Analysis, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Barth","sequence":"additional","affiliation":[{"name":"2 Division of Paediatric Neurology, Emma\u2019s Childrens Hospital, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Kasher","sequence":"additional","affiliation":[{"name":"1 Department of Genome Analysis, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"van Ruissen","sequence":"additional","affiliation":[{"name":"1 Department of Genome Analysis, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Brockmann","sequence":"additional","affiliation":[{"name":"3 Paediatrics and Child Neurology, Georg August University, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnther","family":"Bernert","sequence":"additional","affiliation":[{"name":"4 Kaiser Franz Josef Spital, Sozialmedizinische Zentrum Sud, 1100 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Writzl","sequence":"additional","affiliation":[{"name":"5 Institute Of Medical Genetics, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Ventura","sequence":"additional","affiliation":[{"name":"6 University of Virginia, Department of Obstetrics and Gynaecology, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith Y.","family":"Cheng","sequence":"additional","affiliation":[{"name":"7 Divisions of Maternal Foetal Medicine and Medical Genetics, Departments of Obstetrics and Gynaecology and Internal Medicine, University of Washington, Seattle, WA 98201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Ferriero","sequence":"additional","affiliation":[{"name":"8 Department of Neurology, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Basel-Vanagaite","sequence":"additional","affiliation":[{"name":"9 Schneider Children's Medical Centre of Israel and Raphael Recanati Genetics Institute, Rabin Medical Centre, Petah Tikva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle R. C.","family":"Eggens","sequence":"additional","affiliation":[{"name":"1 Department of Genome Analysis, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg","family":"Kr\u00e4geloh-Mann","sequence":"additional","affiliation":[{"name":"10 Department of Paediatric Neurology and Developmental Medicine, University of T\u00fcbingen, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"De Meirleir","sequence":"additional","affiliation":[{"name":"11 University Hospital, Vrije Universiteit Brussels, 1050 Elsene, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"King","sequence":"additional","affiliation":[{"name":"12 Neurology Department, Children\u2019s University Hospital, Temple Street, Dublin 1, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"John M.","family":"Graham","sequence":"additional","affiliation":[{"name":"13 Medical Genetics Institute, Cedars-Sinai Medical Centre, David Geffen School of Medicine at UCLA, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpad","family":"von Moers","sequence":"additional","affiliation":[{"name":"14 Deutsches Rotes Kreuz Kliniken Berlin Westend, Akademisches Lehrkrankenhaus der Charit\u00e9-Universit\u00e4tsmedizin, 14050 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nine","family":"Knoers","sequence":"additional","affiliation":[{"name":"15 Department of Human Genetics, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo","family":"Sztriha","sequence":"additional","affiliation":[{"name":"16 Department of Paediatrics, Division B, University of Szeged, Szeged, H-6726, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Korinthenberg","sequence":"additional","affiliation":[{"name":"17 University Medical Centre Freiburg, Department of Paediatrics and Adolescent Medicine, Division of Neuropaediatrics and Muscular Disorders, D-79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PCH","family":"Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Dobyns","sequence":"additional","affiliation":[{"name":"18 Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Baas","sequence":"additional","affiliation":[{"name":"1 Department of Genome Analysis, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"19 Department of Neurology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bwee Tien","family":"Poll-The","sequence":"additional","affiliation":[{"name":"2 Division of Paediatric Neurology, Emma\u2019s Childrens Hospital, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,10,15]]},"reference":[{"key":"2022051805112739700_B1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/BF00334450","article-title":"Fatal infantile encephalopathy with olivopontocerebellar hypoplasia, micrencephaly. 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