The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone.
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.
Anttonen
Anna-Kaisa
AK
Folkhälsan Institute of Genetics and Neuroscience Center, University of Helsinki, PO Box 63, FI-00014 Helsinki, Finland.
Mahjneh
Ibrahim
I
Hämäläinen
Riikka H
RH
Lagier-Tourenne
Clotilde
C
Kopra
Outi
O
Waris
Laura
L
Anttonen
Mikko
M
Joensuu
Tarja
T
Kalimo
Hannu
H
Paetau
Anders
A
Tranebjaerg
Lisbeth
L
Chaigne
Denys
D
Koenig
Michel
M
Eeg-Olofsson
Orvar
O
Udd
Bjarne
B
Somer
Mirja
M
Somer
Hannu
H
Lehesjoki
Anna-Elina
AE
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*
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