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

  • Nat Genet. 2005 Dec;37(12):1309-11. doi: 10.1038/ng1677.
Anna-Kaisa Anttonen  1 ,  Ibrahim Mahjneh ,  Riikka H Hämäläinen ,  Clotilde Lagier-Tourenne ,  Outi Kopra ,  Laura Waris ,  Mikko Anttonen ,  Tarja Joensuu ,  Hannu Kalimo ,  Anders Paetau ,  Lisbeth Tranebjaerg ,  Denys Chaigne ,  Michel Koenig ,  Orvar Eeg-Olofsson ,  Bjarne Udd ,  Mirja Somer ,  Hannu Somer ,  Anna-Elina Lehesjoki
Affiliations
  • 1. Folkhälsan Institute of Genetics and Neuroscience Center, University of Helsinki, PO Box 63, FI-00014 Helsinki, Finland.
PMID: 16282978 DOI: 10.1038/ng1677
Abstract

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.