Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy (2005)

Author(s): Senderek J, Krieger M, Stendel C, Bergmann C, Moser M, Breitbach-Faller N, Rudnik-Schoneborn S, Blaschek A, Wolf NI, Harting I, North K, Smith J, Muntoni F, Brockington M, Quijano-Roy S, Renault F, Herrmann R, Hendershot LM, Schroder JM, Lochmuller H, Topaloglu H, Voit T, Weis J, Ebinger F, Zerres K

    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-Sjogren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy. Identification of SIL1 mutations implicates Marinesco-Sjogren syndrome as a disease of endoplasmic reticulum dysfunction and suggests a role for this organelle in multisystem disorders.

      • Date: 13-11-2005
      • Journal: Nature Genetics
      • Volume: 37
      • Issue: 12
      • Pages: 1312-1314
      • Publisher: Nature Publishing Group
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: Adolescent Adult Cataract/ genetics/metabolism Cerebellar Ataxia/ genetics/metabolism Child Child, Preschool Endoplasmic Reticulum/metabolism 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


      Professor Hanns Lochmuller
      Professor of Experimental Myology