Connexin 32 promoter P2 mutations: a mechanism of peripheral nerve dysfunction.
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.
Houlden
Henry
H
Department of Molecular Neurosciences, Institute of Neurology, Queen Square, London, UK. h.houlden@ion.ucl.ac.uk
Girard
Mathilde
M
Cockerell
Charles
C
Ingram
David
D
Wood
Nicholas W
NW
Goossens
Michel
M
Walker
Rodney W H
RW
Reilly
Mary M
MM
D000818:Animals; D019556:COS Cells; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D002522:Chlorocebus aethiops; D017630:Connexins / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006609:High Mobility Group Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D009431:Neural Conduction / Q000235:genetics; D010525:Peripheral Nerves / Q000503:physiopathology*; D011401:Promoter Regions, Genetic; D055757:SOXE Transcription Factors; D012737:Sex Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D014162:Transfection / Q000379:methods; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D004247:DNA; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D055757:SOXE Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D000097002:Gap Junction beta-1 Protein; C072312:ERG protein, human; C527923:SOX10 protein, human