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OBJECTIVE Molecular analysis of hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease (CMT) in the Greek population. METHOD In total, 327 Greek index patients investigated for possible hereditary motor and sensory neuropathy at the Neurogenetics Unit of "Eginition" Hospital over a period of 15 years were included in the study, of which 243 had CMT1, 44 CMT2, and 40 hereditary neuropathy with liability to pressure palsies (HNPP). Mutational analysis was carried out using polymerase chain reaction (PCR) and Sanger sequencing, for the detection of the PMP22 duplication (CMT1A) or deletion (HNPP), and point mutations in GJB1 coding for connexin-32 (CMTX) and MPZ coding for myelin protein zero (CMT1B). In patients with CMT1, sequencing for the detection of point mutations was also carried out in PMP22 (CMT1E), EGR2 (CMT1D), LITAF (CMT1C) and NEFL (CMT1F). RESULTS In patients with CMT1 the mutation frequencies of CMT1A, CMTX, CMT1B, CMT1C, CMT1D, CMT1E and CMT1F were 25.9%, 4.9%, 0.6%, 0%, 0.6%, 1.2% and 0%, respectively. Specifically, in patients with CMT1 10 different GJB1 pathogenic mutations were detected, 5 of them novel (c.110T>C, c.208C>T, c.462T>G, c.109G>T, c.42-43insT), one novel MPZ mutation (c.89T>C), two novel PMP22 micromutations (c.296_301del CTGGAA, c.328_348dup21) and one known EGR2 mutation. In patients with CMT2, two cases were detected with the PMP22 duplication and two with a novel mutation in GJB1 (c.524A>G). The PMP22 deletion was present in 30% of the patients with HNPP. CONCLUSIONS In the Greek population, among the genetic subtypes of CMT investigated, CMT1A is the most common, followed by CMTX. CMT1E, CMT1B and CMT1D appear to be rare. The CMT1A duplication frequency is significantly lower in Greek patients with CMT than most other European populations. This may imply a special genetic characteristic of the Greek population, possibly resulting from partial genetic isolation. The frequencies of CMTX, CMT1E and CMT1D in Greek patients with CMT1 are similar to those reported in other ethnic populations. The overall frequency of MPZ mutation in Greek patients with CMT1 is one of the lowest observed to date. The PMP22 deletion frequency appears to be lower in Greek patients with HNPP than in other European populations. The absence of CMT1C and 1F in Greek patients with CMT1 is not a surprise given the rarity of these mutations in other populations. [ABSTRACT FROM AUTHOR]