A novel Cx32 mutation causes X-linked Charcot-Marie-Tooth disease with brainstem involvement and brain magnetic resonance spectroscopy abnormalities

Neurol Sci. 2006 Apr;27(1):18-23. doi: 10.1007/s10072-006-0560-8.

Abstract

The objective of this study was to study genetic and phenotypic features of a family with X-linked Charcot-Marie-Tooth consisting of a healthy father, affected mother, two affected sons and one healthy one. A detailed electrophysiological and neuroimaging study, along with sequencing of the Cx32 gene, was performed in all family members. A novel Cx32 123 G>C mutation, determining an aminoacid variation (Glu41Asp), was found in the mother and the affected sons. An alteration in brainstem evoked potentials was found in the mother and one affected son. The affected son, who underwent magnetic resonance imaging, showed symmetrical hyperintensities in paratrigonal white matter, not found in his heterozygous mother, while both subjects exhibited alterations in brain metabolite ratios derived from localised proton-magnetic resonance spectroscopy. These data extend previous findings about central nervous system involvement in Cx32 mutated subjects and further support a functional role of the protein expression in oligodendrocytes.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Brain Chemistry / genetics
  • Brain Stem / metabolism
  • Brain Stem / pathology
  • Brain Stem / physiopathology*
  • Charcot-Marie-Tooth Disease / diagnosis
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / physiopathology
  • Connexins / genetics*
  • Creatinine / metabolism
  • DNA Mutational Analysis
  • Evoked Potentials / genetics
  • Female
  • Gap Junction beta-1 Protein
  • Genetic Diseases, X-Linked / diagnosis
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / physiopathology
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Humans
  • Lateral Ventricles / pathology
  • Linkage Disequilibrium / genetics
  • Magnetic Resonance Spectroscopy
  • Mutation, Missense / genetics*
  • Nerve Fibers, Myelinated / pathology
  • Neural Conduction / genetics
  • Neural Pathways / pathology
  • Neural Pathways / physiopathology
  • Pedigree
  • Telencephalon / metabolism
  • Telencephalon / pathology
  • Telencephalon / physiopathology

Substances

  • Connexins
  • Aspartic Acid
  • N-acetylaspartate
  • Creatinine