A French retrospective analysis studied genotype/phenotype correlations in 275 adults with Charcot-Marie-Tooth X1 (CMT X1) disease managed in the 13 largest neuromuscular disease reference centres.
- Patients were classified into three categories according to the protein domain affected by the mutation in the GJB1 gene encoding connexin 32: transmembrane domain (25 variants for 72 patients), extracellular domain (26 variants for 94 patients) and intracellular domain (22 variants for 64 patients).
- The severity of the disease, assessed using the CMTES (Charcot-Marie-Tooth Examination Score), revealed a score of 10.5 for the transmembrane domain, 8.7 for the extracellular domain and 7.1 for the intracellular domain.
- The Overall Neuropathy Limitation Score (ONLS) correlated well with the CMTES score.
- Other criteria, such as the age of onset of the first signs of the disease and electrophysiological criteria, were consistent with these results.
These results will help clinicians to form more homogeneous and comparable groups for future clinical trials, and are also useful for genetic counselling.
