Background: Mutations of the peripheral myelin protein zero (MPZ, P0) gene have been for 10 years one of the known causes of the demyelination type of Charcot-Marie-Tooth (CMT) disease, which in addition to the classical CMT1 form also includes the early onset and severe form of Déjerine-Sottas neuropathy (DSS) and yet earlier onset and more severe congenital hypomyelinating neuropathy (CHN). P0 protein is the main component of peripheral myelin and plays a crucial role in the process of peripheral myelination. In the last few years, families with axonal type of CMT due to P0 gene mutations have been described. Patients and Results:We describe 3 Czech families with proven P0 gene mutations and completely different times of onset, clinical courses and forms of the CMT disease. The mutations found have been reported previously in other countries. Arg98Cys was found in two families with three affected members, once in 2 generations, with a severe demyelinating form, childhood onset and stable course and with extremely low peripheral nerve conduction velocity, and next, Thr124Met mutation in a female patient with late onset of axonal form of CMT disease at the end of the fourth decade, abnormal pupillary reaction and relatively rapid progression of disease. Arg98Cys mutation occurred in both families de novo, in the Thr124Met mutation, patient’s parents could not be investigated but the patient’s mother has a history compatible with CMT disease. Both son and daughter of the patient have presently no clinical signs of polyneuropathy but have abnormal pupillary reaction. The son has the same mutation, daughter has not been investigated yet. Conclusions: Severe demyelinating hereditary neuropathy with childhood onset (DSS) and axonal late-onset CMT2 represent the opposite ends of the spectrum of myelination disorder caused by P0 gene mutations. The 98 Arg codon of the P0 gene is a locus of repeated occurrence of mutations found also in Czech families. Elucidation of the reason why some P0 gene mutations lead to very early-onset demyelinating neuropathy and other mutations of the same gene lead to late-onset axonal neuropathy could offer a clue to molecular interactions between the axon and the Schwann cell.

        Key words: HMSN III, Déjerine-Sottas, P0, MPZ, myelin protein zero, Charcot-Marie-Tooth, CMT