Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy.
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-Sjögren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy. Identification of SIL1 mutations implicates Marinesco-Sjögren syndrome as a disease of endoplasmic reticulum dysfunction and suggests a role for this organelle in multisystem disorders.
Senderek
Jan
J
Department of Human Genetics, Aachen University of Technology, Aachen, Germany. jsenderek@ukaachen.de
Krieger
Michael
M
Stendel
Claudia
C
Bergmann
Carsten
C
Moser
Markus
M
Breitbach-Faller
Nico
N
Rudnik-Schöneborn
Sabine
S
Blaschek
Astrid
A
Wolf
Nicole I
NI
Harting
Inga
I
North
Kathryn
K
Smith
Janine
J
Muntoni
Francesco
F
Brockington
Martin
M
Quijano-Roy
Susana
S
Renault
Francis
F
Herrmann
Ralf
R
Hendershot
Linda M
LM
Schröder
J Michael
JM
Lochmüller
Hanns
H
Topaloglu
Haluk
H
Voit
Thomas
T
Weis
Joachim
J
Ebinger
Friedrich
F
Zerres
Klaus
K
D000293:Adolescent; D000328:Adult; D002386:Cataract / Q000235:genetics* / Q000378:metabolism; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome
D000091342:Endoplasmic Reticulum Chaperone BiP; D020662:Guanine Nucleotide Exchange Factors; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C418483:SIL1 protein, human