Phenotypic expression of a Pro 87 to Leu mutation in the connexin 32 gene in a large Swiss family with Charcot-Marie-Tooth neuropathy

Détails

ID Serval
serval:BIB_7452839B3340
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Phenotypic expression of a Pro 87 to Leu mutation in the connexin 32 gene in a large Swiss family with Charcot-Marie-Tooth neuropathy
Périodique
Journal of the Neurological Sciences
Auteur(s)
Kuntzer  T., Dunand  M., Schorderet  D. F., Vallat  J. M., Hahn  A. F., Bogousslavsky  J.
ISSN
0022-510X (Print)
Statut éditorial
Publié
Date de publication
03/2003
Peer-reviewed
Oui
Volume
207
Numéro
1-2
Pages
77-86
Notes
Comparative Study Journal Article Research Support, Non-U.S. Gov't --- Old month value: Mar 15
Résumé
BACKGROUND: The clinical manifestations of CMTX have been well described but the natural history has not yet been studied in detail. We studied phenotype variability in a family with a Pro 87 to Leu mutation of the connexin 32 (Cx32) gene. METHODS: A total of 32 family members, of which 19 patients were affected, underwent clinical, electrophysiological, and genetic studies. RESULTS: Onset was in the second decade. Clinical features were similar in both sexes when quantitative scores were compared, but more males had a steppage gait and skeletal deformities. All adult patients had a predominant involvement of the thenar muscles. The median values of nerve conduction velocities (NCVs) were not statistically different in men and in women. The correlation coefficients were low between motor NCVs within the same extremities, indicating nonuniform slowing between nerves, the ulnar nerve being the least affected. When disability was rated, a strong correlation was seen in male patients between severity of motor axonal loss and duration of the disease. The main pathological features were axonal loss, clusters of regenerating fibers and paranodal demyelination, the hallmark of a Schwann cell pathology. CONCLUSIONS: Our data support the hypothesis that clinical disability in CMTX is caused by loss of large myelinated axons in men. Furthermore, this study shows that the nerves are not uniformly affected in terms of axonal loss. Preventing axonal degeneration and promoting axonal regeneration in the most affected nerves might be the best therapeutic approaches to ameliorate disability in CMTX.
Mots-clé
Adolescent Adult Aged Amino Acid Substitution/*genetics Charcot-Marie-Tooth Disease/*genetics/physiopathology Child Child, Preschool Connexins/*genetics Female Humans Leucine/*genetics Male Middle Aged Neural Conduction/genetics Pedigree Phenotype *Point Mutation Statistics, Nonparametric
Pubmed
Web of science
Création de la notice
28/01/2008 13:58
Dernière modification de la notice
03/03/2018 18:21
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