THE MOST FREQUENT TYPES OF DEMYELINATIVE CHARCOT-MARIE-TOOTH DISEASE IN SLOVENIA: A POPULATION-BASED STUDY
Keywords:
hereditary diseases, incidence, prevalence, polyneuropathiesAbstract
Background. The most common genetic defect in demyelinative type of Charcot-Marie-Tooth disease (CMT1) is dominantly inherited duplication of 17p11.2 (CMT1A). Phenotipically rather different, but genetically related to CMT1A, is hereditary neuropathy with liability to pressure palsies (HNPP) which is linked to deletion of the same part of chromosome 17 as duplication in CMT1A. The aim of our study was to analyse the frequency of duplication and deletion of 17p11.2 in CMT1 and HNPP Slovene patients, respectively. We also sought for eventual point mutations in connexin-32 (Cx32), protein zero (P0), peripheral myelin protein-22 (PMP22) genes and in N-myc downstream-regulated gene1 (NDRG1).
Methods. Probes pVAW409R3a, pNEA102 and pLR7.8 were used for Southern blotting and primers RM-11 in Mfd-41 for the polymerase chain reaction. Sequencing was used for the demonstration of eventual point mutations.
Results and conclusions. The duplication or deletion of 17p11.2 was found in 76% and 100% of unrelated CMT1 and HNPP patients, respectively. Point mutations in P0 were found in 8% of unrelated patients. In a Gypsy family, point mutation in NDRG1 was revealed. The prevalence of CMT1A in Slovenia was found to be 4.7/100,000 which is most likely less than true average (10/100,000 elsewhere). The Slovene prevalence of HNPP was calculated at 2,2/100,000 (2–16/100.000 elsewhere).
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