Journal Article

The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone

Udd, Bjarne, Kopra, Outi, Koenig, Michel, Anttonen, Anna-Kaisa, Chaigne, Denys, Tranebjaerg, Lisbeth, Eeg-Olofsson, Orvar, Lagier-Tourenne, Clotilde, Joensuu, Tarja, Somer, Mirja, Mahjneh, Ibrahim, Somer, Hannu, Waris, Laura, Kalimo, Hannu, Hämäläinen, Riikka H, Lehesjoki, Anna-Elina, Paetau, Anders, Anttonen, Mikko

2005

Overview

We identified the gene underlying Marinesco-Sjögren syndrome, which is characterized by cerebellar ataxia, progressive myopathy and cataracts. We identified four disease-associated, predicted loss-of-function mutations in SIL1 , which encodes a nucleotide exchange factor for the heat-shock protein 70 (HSP70) chaperone HSPA5. These data, together with the similar spatial and temporal patterns of tissue expression of Sil1 and Hspa5, suggest that disturbed SIL1-HSPA5 interaction and protein folding is the primary pathology in Marinesco-Sjögren syndrome.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Agriculture / Animal Genetics and Genomics / Ataxia / Biochemistry, Molecular Biology / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / brief-communication / Cancer Research / Cataracts / Cerebrospinal fluid. Meninges. Spinal cord / Complications and side effects / Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases / Diagnosis / DNA sequencing / Finland / Fundamental and applied biological sciences. Psychology / Gene Deletion / Gene Function / Gene mutations / Genetic disorders / Genetics of eukaryotes. Biological and molecular evolution / Guanine Nucleotide Exchange Factors / Guanine Nucleotide Exchange Factors - analysis / Guanine Nucleotide Exchange Factors - genetics / Guanine Nucleotide Exchange Factors - metabolism / Guanine Nucleotide Exchange Factors/analysis/genetics/metabolism / Haplotypes / Health aspects / Heat-Shock Proteins / Heat-Shock Proteins - metabolism / Hospitals / Human Genetics / Humans / Life Sciences / Medical sciences / Methods / Molecular biology / Molecular Chaperones / Molecular Chaperones - metabolism / Muscle, Skeletal / Muscle, Skeletal - chemistry / Mutation / Nervous system (semeiology, syndromes) / Neurology / Nucleotide sequencing / Pathology / Protein Folding / Proteins / Proteins - metabolism / Risk factors / Spinocerebellar Degenerations / Spinocerebellar Degenerations - genetics / Spinocerebellar Degenerations - metabolism / Spinocerebellar Degenerations/genetics/metabolism