Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy

  • Nat Genet. 2005 Dec;37(12):1312-4. doi: 10.1038/ng1678.
Jan Senderek  1 ,  Michael Krieger ,  Claudia Stendel ,  Carsten Bergmann ,  Markus Moser ,  Nico Breitbach-Faller ,  Sabine Rudnik-Schöneborn ,  Astrid Blaschek ,  Nicole I Wolf ,  Inga Harting ,  Kathryn North ,  Janine Smith ,  Francesco Muntoni ,  Martin Brockington ,  Susana Quijano-Roy ,  Francis Renault ,  Ralf Herrmann ,  Linda M Hendershot ,  J Michael Schröder ,  Hanns Lochmüller ,  Haluk Topaloglu ,  Thomas Voit ,  Joachim Weis ,  Friedrich Ebinger ,  Klaus Zerres
Affiliations
  • 1. Department of Human Genetics, Aachen University of Technology, Aachen, Germany. [email protected]
PMID: 16282977 DOI: 10.1038/ng1678
Abstract

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.