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

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.

• Authors: Jan Senderek, 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
• Journal: Nature genetics (Nat Genet) Vol. 37 Issue 12 Pg. 1312-4 (Dec 2005) ISSN: 1061-4036 [Print] United States
• PMID: 16282977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• Guanine Nucleotide Exchange Factors
• HSPA5 protein, human
• Heat-Shock Proteins
• Molecular Chaperones
• SIL1 protein, human

Topics

• Adolescent
• Adult
• Cataract (genetics, metabolism)
• Cerebellar Ataxia (genetics, metabolism)
• Child
• Child, Preschool
• Endoplasmic Reticulum (metabolism)
• Endoplasmic Reticulum Chaperone BiP
• Female
• Guanine Nucleotide Exchange Factors (chemistry, genetics, metabolism)
• Heat-Shock Proteins (metabolism)
• Humans
• Male
• Molecular Chaperones (metabolism)
• Muscular Diseases (genetics, metabolism)
• Mutation
• Spinocerebellar Degenerations (genetics, metabolism)
• Syndrome