Abstract
We identified a large Charcot-Marie-Tooth disease family with a novel mutation in the Connexin 32 (Cx32) P2 promoter region at position -526bp. This mutation was in a highly conserved SOX10 binding site. Functional studies were conducted on the Cx32 promoter that showed that this mutation reduced the activity of the Cx32 promoter and the affinity for SOX10 binding. These data suggest that interaction between the Cx32 P2 promoter, SOX10, and EGR2 highlight a mechanism of peripheral nerve dysfunction.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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COS Cells
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Charcot-Marie-Tooth Disease / genetics*
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Charcot-Marie-Tooth Disease / physiopathology
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Chlorocebus aethiops
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Connexins / genetics*
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DNA / metabolism
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DNA-Binding Proteins / metabolism
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Electrophoretic Mobility Shift Assay / methods
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Family Health
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Female
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Gap Junction beta-1 Protein
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Genetic Linkage
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High Mobility Group Proteins / metabolism
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Humans
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Male
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Mutation*
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Neural Conduction / genetics
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Peripheral Nerves / physiopathology*
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Promoter Regions, Genetic*
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SOXE Transcription Factors
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Sex Factors
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Trans-Activators / metabolism
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Transcription Factors
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Transcriptional Regulator ERG
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Transfection / methods
Substances
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Connexins
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DNA-Binding Proteins
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ERG protein, human
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High Mobility Group Proteins
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SOX10 protein, human
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SOXE Transcription Factors
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Trans-Activators
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Transcription Factors
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Transcriptional Regulator ERG
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DNA