Nature Genetics 37, 1312 - 1314 (2005)
Published online: 13 November 2005; | doi:10.1038/ng1678
Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathyJan Senderek1, Michael Krieger1, Claudia Stendel1, Carsten Bergmann1, Markus Moser2, Nico Breitbach-Faller3, Sabine Rudnik-Schöneborn1, Astrid Blaschek4, Nicole I Wolf4, Inga Harting5, Kathryn North6, Janine Smith6, Francesco Muntoni7, Martin Brockington7, Susana Quijano-Roy8, Francis Renault9, Ralf Herrmann10, Linda M Hendershot11, J Michael Schröder12, Hanns Lochmüller13, Haluk Topaloglu14, Thomas Voit10, Joachim Weis12, Friedrich Ebinger4
& Klaus Zerres11
Department of Human Genetics, Aachen University of Technology, Aachen, Germany. 2
Max-Planck-Institute of Biochemistry, Martinsried, Germany. 3
Department of Pediatrics, Esslingen Community Hospital, Esslingen, Germany. 4
Department of Pediatric Neurology, University Children's Hospital Heidelberg, Heidelberg, Germany. 5
Department of Neuroradiology, University of Heidelberg, Heidelberg, Germany. 6
Institute for Neuromuscular Research, Children's Hospital at Westmead, Westmead, Sydney, Australia. 7
Dubowitz Neuromuscular Centre, Imperial College London, Hammersmith Hospital Campus, London, UK. 8
Service de Pédiatrie, Hôpital Raymond-Poincaré, Garches; INSERM U582, Institut de Myologie, IFR 14, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. 9
Unité de Neurophysiologie, Hôpital d'Enfants Armand-Trousseau, Paris, France. 10
Department of Pediatrics and Pediatric Neurology, University Hospital Essen, Essen, Germany. 11
Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. 12
Department of Neuropathology, Aachen University of Technology, Aachen, Germany. 13
Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University, München, Germany. 14
Department of Pediatric Neurology, Hacettepe University, Ankara, Turkey.
Correspondence should be addressed to Jan Senderek jsenderek@ukaachen.de SIL1 (also called BAP) acts as a nucleotide exchange factor for the Hsp70 chaperone BiP (also called GRP78), which is a key regulator of the main functions of the endoplasmic reticulum. We found nine distinct mutations that would disrupt the SIL1 protein in individuals with Marinesco-Sjögren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy. Identification of SIL1 mutations implicates Marinesco-Sjögren syndrome as a disease of endoplasmic reticulum dysfunction and suggests a role for this organelle in multisystem disorders.
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