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Connexin 32 promoter P2 mutations: A mechanism of peripheral nerve dysfunction
Author(s) -
Houlden Henry,
Girard Mathilde,
Cockerell Charles,
Ingram David,
Wood Nicholas W.,
Goossens Michel,
Walker Rodney W. H.,
Reilly Mary M.
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20267
Subject(s) - sox10 , connexin , connexin 32 , mutation , mechanism (biology) , genetics , biology , promoter , microbiology and biotechnology , gene , gap junction , transcription factor , gene expression , philosophy , intracellular , epistemology
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. Ann Neurol, 2004