Author/Editor		Leonardis, Lea; Zidar, Janez; Peterlin, Borut
Title		Populacijska študija najpogostejših demielinizacijskih bolezni Charcot-Marie-Tooth v Sloveniji
Translated title		The most frequent types of demyelinative Charot-Marie-Tooth disease in Slovenia: a population-based study
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 72, št. 10
Publication year		2003
Volume		str. 561-5
Language		slo
Abstract		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 and deletion 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. In a 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 than true average (10/100,000 elsewhere). The Slovene prevalence of HNPP was calculated at 2,2/100,000 (2-16/100.000 elsewhere).
Summary		Izhodišča. Demielinizacijska oblika bolezni Charcot-Marie-Tooth (CMTI) nastane najpogosteje 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 17p11.2 smo 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).
Descriptors		CHARCOT-MARIE DISEASE CHROMOSOMES, HUMAN, PAIR 17 CHROMOSOME DELETION POINT MUTATION GENES, MYC INCIDENCE PREVALENCE SLOVENIA CONNEXINS MYELIN P0 PROTEIN MYELIN PROTEINS BLOTTING, SOUTHERN POLYMERASE CHAIN REACTION