Neurobiology of Disease (Aug 2001)
The D355V Mutation Decreases EGR2 Binding to an Element within the Cx32 Promoter
- Marco Musso,
- Piercesare Balestra,
- Emilia Bellone,
- Denise Cassandrini,
- Emilio Di Maria,
- Laura Lamba Doria,
- Marina Grandis,
- GianLuigi Mancardi,
- Angelo Schenone,
- Giovanni Levi,
- Franco Ajmar,
- Paola Mandich
Affiliations
- Marco Musso
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Piercesare Balestra
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Emilia Bellone
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Denise Cassandrini
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Emilio Di Maria
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Laura Lamba Doria
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Marina Grandis
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- GianLuigi Mancardi
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Angelo Schenone
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Giovanni Levi
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Franco Ajmar
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Paola Mandich
- Department of Neurological Sciences and Vision, University of Genova, Viale Benedetto XV, 6-16132, Genova, Italy; Service of Medical Genetics, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova, Italy; Laboratory of Molecular Morphogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Journal volume & issue
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Vol. 8,
no. 4
pp. 700 – 706
Abstract
Mutations in the early growth response 2 (EGR2) gene are associated with some forms of Charcot–Marie–Tooth disease (CMT) and other demyelinating neuropathies. These mutations modify the EGR2 binding to specific DNA sequences suggesting a role in the transcriptional control of myelination-specific genes. Here we show that the D355V mutation, associated with a CMT case combining axonal and demyelinating abnormalities, reduces three times the affinity of EGR2 to its consensus sequence and ten times its affinity to a sequence in the human Cx32 promoter. These findings could indicate that this EGR2 mutation leads to the development of CMT1 through the transcriptional deregulation of Cx32 gene.
