title: The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone.
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.
authors.affiliation: Folkhälsan Institute of Genetics and Neuroscience Center, University of Helsinki, PO Box 63, FI-00014 Helsinki, Finland.
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Anttonen
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Mahjneh
authors.forename: Riikka H
authors.initials: RH
authors.lastname: Hämäläinen
authors.forename: Clotilde
authors.initials: C
authors.lastname: Lagier-Tourenne
authors.forename: Outi
authors.initials: O
authors.lastname: Kopra
authors.forename: Laura
authors.initials: L
authors.lastname: Waris
authors.forename: Mikko
authors.initials: M
authors.lastname: Anttonen
authors.forename: Tarja
authors.initials: T
authors.lastname: Joensuu
authors.forename: Hannu
authors.initials: H
authors.lastname: Kalimo
authors.forename: Anders
authors.initials: A
authors.lastname: Paetau
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: Denys
authors.initials: D
authors.lastname: Chaigne
authors.forename: Michel
authors.initials: M
authors.lastname: Koenig
authors.forename: Orvar
authors.initials: O
authors.lastname: Eeg-Olofsson
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
authors.forename: Mirja
authors.initials: M
authors.lastname: Somer
authors.forename: Hannu
authors.initials: H
authors.lastname: Somer
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
mesh_terms: D000091342:Endoplasmic Reticulum Chaperone BiP; D005387:Finland; D017353:Gene Deletion; D020662:Guanine Nucleotide Exchange Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry; D009154:Mutation; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism*; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D020662:Guanine Nucleotide Exchange Factors; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011506:Proteins; C418483:SIL1 protein, human