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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Cataract / genetics*
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Cataract / metabolism
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Cerebellar Ataxia / genetics*
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Cerebellar Ataxia / metabolism
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Child
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Child, Preschool
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Endoplasmic Reticulum / metabolism
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Endoplasmic Reticulum Chaperone BiP
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Female
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Guanine Nucleotide Exchange Factors / chemistry
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Guanine Nucleotide Exchange Factors / genetics*
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Guanine Nucleotide Exchange Factors / metabolism
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Heat-Shock Proteins / metabolism
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Humans
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Male
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Molecular Chaperones / metabolism
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Muscular Diseases / genetics*
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Muscular Diseases / metabolism
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Mutation
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Spinocerebellar Degenerations / genetics*
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Spinocerebellar Degenerations / metabolism
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Syndrome
Substances
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Endoplasmic Reticulum Chaperone BiP
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Guanine Nucleotide Exchange Factors
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HSPA5 protein, human
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Heat-Shock Proteins
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Molecular Chaperones
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SIL1 protein, human
Associated data
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OMIM/246700
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OMIM/248800
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OMIM/604168