Hereditary Charcot-Marie-Tooth disease (CMT) type sensorimotor neuropathies are clinically and genetically heterogeneous diseases. They are relatively common in the general population, and result in motor deficit in the extremities varying in severity and speed of progression, combined with sensory disorders that are rarely prominent. Almost 100 genes, of autosomal dominant or recessive inheritance or X-linked dominant inheritance, are responsible for this condition, whether it is the demyelinating (CMT1) or axonal (CMT2) form.
In an article published in May 2021, an international consortium of researchers reported the involvement, in three unrelated families, of a same pathogenic variant (Tyr172Cys) inside the CADM3 gene, coding a cell adhesion protein. This protein belongs to a broader family of proteins involved in interactions between glial cells and neurons. This work is the result of a next-generation sequencing (NGS) study based on unresolved axonal CMT cases. This variant has been the subject of several very convincing functional studies involving mice and mass spectrometry. Phenotypically, the profile matched that of the axonal form, with motor deficit most prevalent in the upper limbs. In addition, certain patients presented signs of upper motor neuron involvement.