Involvement of myelin proteins in hereditary neuropathies.

Hereditary sensoro-motor neuropathies such as Charcot-Marie-Tooth disease ( CMT) form a heterogeneous group including some genetic conditions whose cli nical manifestations differ in severity within a group or even within a sub -group. Diagnosis is based on the clinical, electrophysiological and pathol ogical findings along with a genetic analysis. The current classification o f CMT encompasses the clinical signs, mode of transmission, genomic localiz ation and identification of the proteins actually involved. Several authors have identified the mutations on genes coding for proteins of peripheral m yelin in CMT patients. Recent advances in molecular genetics have thrown mo re light on the differences between phenotypes within a sub-group, and have established genotype-phenotype relationships. It has been shown recently t hat the severity of the clinical signs depends on the nature and site of va rious mutations affecting the genes coding for certain myelin proteins. The se mutations give rise to "dominant negative effects" or "mutations with lo ss of function of the allele". These observations may be extended to other proteins as many of them belong to the super family of immunoglobulins and have similar structures. In this study, we present a review of the literature focussing on the princ ipal myelin proteins and the genomic modifications observed in patients wit h CMT.