Letter abstract
Nature Genetics 40, 1113 - 1118 (2008)
Published online: 17 August 2008 | doi:10.1038/ng.204
tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia
Birgit S Budde1,32, Yasmin Namavar2,3,32, Peter G Barth3, Bwee Tien Poll-The3, Gudrun Nürnberg1, Christian Becker1, Fred van Ruissen2, Marian A J Weterman2, Kees Fluiter2, Erik T te Beek2, Eleonora Aronica4, Marjo S van der Knaap5, Wolfgang Höhne6, Mohammad Reza Toliat1, Yanick J Crow7, Maja Steinlin8, Thomas Voit9, Filip Roelens10, Wim Brussel11, Knut Brockmann12, Marten Kyllerman13, Eugen Boltshauser14, Gerhard Hammersen15, Michèl Willemsen16, Lina Basel-Vanagaite17, Ingeborg Krägeloh-Mann18, Linda S de Vries19, Laszlo Sztriha20, Francesco Muntoni21, Colin D Ferrie22, Roberta Battini23, Raoul C M Hennekam21,24, Eugenio Grillo25, Frits A Beemer26, Loes M E Stoets27, Bernd Wollnik28,29,30,31, Peter Nürnberg1,28,29 & Frank Baas2
Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.
- Cologne Center for Genomics and Institute for Genetics, University of Cologne, Zülpicher Strasse 47, D-50674 Cologne, Germany.
- Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Division of Pedriatric Neurology, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Department of Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
- Department of Pediatrics and Child Neurology, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
- Institut für Biochemie, Charité-Universitätsmedizin Berlin, Monbijoustrasse 2, D-10117, Berlin, Germany.
- Leeds Institute of Molecular Medicine, St. James's University Hospital, Leeds, West Yorkshire LS9 7TF, UK.
- Department of Pediatric Neurology, University Hospital Bern, 3010 Bern, Switzerland.
- Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.
- Department of Pediatrics, Heilig Hartziekenhuis, Wilgenstraat 2, 8800 Roeselare, Belgium.
- Department of Pediatrics, Rijnstate Hospital, Wagnerlaan 55, 6815 AD Arnhem, The Netherlands.
- Department of Paediatrics and Child Neurology, Georg August University, 37075 Göttingen, Germany.
- Department of Paediatrics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, S-41685 Göteborg, Sweden.
- University Children's Hospital, Steinwiesstrasse 75, 8032 Zürich, Switzerland.
- CNOPF'sche Kinderklinik, St. Johannis Mühlgasse 19, 90419 Nürnberg, Germany.
- Department of Pediatric Neurology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
- Schneider Children's Medical Center of Israel and Raphael Recanati Genetic Institute, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel.
- Department of Paediatric Neurology and Developmental Medicine, University of Tübingen, Hoppe Seyler Strasse 1, D-72076 Tübingen, Germany.
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center, Lundlaan 6, 3584 AE Utrecht, The Netherlands.
- Department of Paediatrics, University of Szeged, Temesvári krt. 35-37, Szeged H-6726, Hungary.
- Institute of Child Health, Great Ormond Street Hospital for Children, University College London, 30 Guilford Street, London WC1N 1EH, UK.
- Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK.
- Division of Child Neurology and Psychiatry, University of Pisa - Stella Maris Scientific Institute, Via dei Giacinti, 1, I-56018 Calambrone Pisa, Italy.
- Department of Pediatrics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
- Department of Neurology, Hospital Infantil Joana de Gusmão, Rua Rui Barbosa 152, 88025-301 Florianópolis, Santa Catarina, Brazil.
- Department of Medical Genetics, University Medical Center Utrecht, Lundlaan 6, 3584 AE Utrecht, The Netherlands.
- Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Zülpicher Strasse 47, 50674 Cologne, Germany.
- Center for Molecular Medicine Cologne, Josef-Stelzmann-Strasse 9, 50931 Cologne, Germany
- Institute of Human Genetics; University of Cologne, Josef-Stelzmann-Strasse 9, 50931 Cologne, Germany.
- Medical Genetics Department, Istanbul Medical Faculty, Istanbul University, 34390 Istanbul, Turkey.
- These authors contributed equally to this work.
Correspondence to: Frank Baas2 e-mail: f.baas@amc.uva.nl
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
tRNA splicing endonuclease mutations cause pontocerebellar hypoplasiaNature Genetics Letter (01 Sep 2008)
