title: Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy.
abstract: 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.
authors.affiliation: Department of Human Genetics, Aachen University of Technology, Aachen, Germany. jsenderek@ukaachen.de
authors.forename: Jan
authors.initials: J
authors.lastname: Senderek
authors.forename: Michael
authors.initials: M
authors.lastname: Krieger
authors.forename: Claudia
authors.initials: C
authors.lastname: Stendel
authors.forename: Carsten
authors.initials: C
authors.lastname: Bergmann
authors.forename: Markus
authors.initials: M
authors.lastname: Moser
authors.forename: Nico
authors.initials: N
authors.lastname: Breitbach-Faller
authors.forename: Sabine
authors.initials: S
authors.lastname: Rudnik-Schöneborn
authors.forename: Astrid
authors.initials: A
authors.lastname: Blaschek
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
authors.forename: Inga
authors.initials: I
authors.lastname: Harting
authors.forename: Kathryn
authors.initials: K
authors.lastname: North
authors.forename: Janine
authors.initials: J
authors.lastname: Smith
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Martin
authors.initials: M
authors.lastname: Brockington
authors.forename: Susana
authors.initials: S
authors.lastname: Quijano-Roy
authors.forename: Francis
authors.initials: F
authors.lastname: Renault
authors.forename: Ralf
authors.initials: R
authors.lastname: Herrmann
authors.forename: Linda M
authors.initials: LM
authors.lastname: Hendershot
authors.forename: J Michael
authors.initials: JM
authors.lastname: Schröder
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Friedrich
authors.initials: F
authors.lastname: Ebinger
authors.forename: Klaus
authors.initials: K
authors.lastname: Zerres
mesh_terms: 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
chemical_list: 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