29 KB520 KB28 KB192920262003Leonardis, LeaPeterlin, BorutZidar, Janezštevilka:10letnik:72str. 561-565ISSN:1318-0347COBISSID:17094617URN:URN:NBN:SI:doc-PUNQVDWEslSlovensko zdravniško društvoZdravniški vestnikBlot, SouthernBlotting, SouthernCharcot-Marie DiseaseChromosome DeletionChromosomes, Human, Pair 17Connexinsdedne bolezniEpidemiologyGenes, MycGeneticsGeni mycIncidencaIncidenceKoneksiniKromosomi človeški, par 17Kromosomska delecijaMielinska P0 beljakovinaMielinske beljakovinemutacijeMyelin P0 ProteinMyelin Proteinsperiferno živčevjePoint MutationPolimerazna, verižna reakcijaPolymerase Chain ReactionPrevalencaPrevalenceTočkovna mutacijaPopulacijska študija najpogostejših demielinizacijskih bolezni Charcot-Marie-Tooth v Sloveniji| The most frequent types of demyelinative Charot-Marie-Tooth disease in Slovenia|Background. The most common genetic defect in demyelinative type of Charcot-Marie-Tooth disease (CMTI) is dominantly inherited duplication of 17p11.2 (CMT1A). Phenotipically rather different, butgenetically related to CMTIA, is hereditary neuropathy with liability to pressure palsies (HNPP) which is linked to deletion of the same part of chromosome 17 as duplication in CMTIA. The aim of our study was to analyse the frequency of duplication anddeletion of Z7p11.2 in CMTI 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 genel (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 ordeletion of 17p11.2 was found in 76% and 100% of unrelated CMTI and HNPP patients, respectively. Point mutations in P0 were found in 8% of unrelated patients. Ina Gypsy family, point mutation in NDRGI was revealed. The prevalence of CMTIA in Slovenia was found to be 4. 7/100, 000 which is most likely less thantrue average (10/100,000 elsewhere). The Slovene prevalence of HNPP was calculated at 2,2/100,000 (2-16/100.000 elsewhere)Izhodišča. Demielinizacijska oblika bolezni Charcot-Marie-Tooth (CMTI) nastanenajpogosteje zaradi podvojitve kromosomskega odseka 17p11.2 (CMT1A). Klinično različna, genetsko pa s CMTIA povezana demielinizacijska bolezen je dedna nagnjenost h kompresijskim parezam (DNKP), ki je posledica delecije istega dela 17 kromosoma. Želeli smo ugotoviti, kako pogosti sta ti dve mutaciji pri slovenskih bolnikih, kolikokrat pa so vzrok bolezni točkaste mutacije v genih za koneksin 32 (Cx32), protein nič (P0, periferni mielinski protein 22 (PMP22) in v N-myc navzdol urejanem genu 1 (NDRGI). Metode. Podvojitev in delecijo 17p11.2 smo ugotavljali s sondami pLR7.8, pNEA102 in pVAW409R3a ter z začetnimi oligonukleotidi RM-11 in Mfd-41. Točkaste mutacije smo dokazovali s sekvencioniranjem. Rezultati in zaključki. Podvojitev 17p11.2smo dokazali pri 76% bolnikov s CMTI iz različnih družin, delecijo pa pri vseh pregledanih bolnikih z DNKP. Pri 8% družin smo odkrili točkasto mutacijo na P0. Pri romski družini smo ugotovili mutacijo na NDRGZ Prevalenca CMTIA v Sloveniji je po naši oceni 4,1/100.000 prebivalcev, kar je ob upoštevanju omejitev študije najverjetneje manj od dejanske (okrog 10/100.000 po virih za neketere druge populacije). Prevalenco DNKP ocenjujemo na 2,2 na 100.000 prebivalcev (tuja literatura: 216/100.000)TEXTznanstveno časopisjejournalsSlovenian National E-content AggregatorNational and University Library of SloveniaSlovensko zdravniško društvo