Molecular diagnosis of Huntington's disease

Huntingtonova bolest (HB) je autosomno dominantna neurodegenerativna bolest koja dovodi do karakterističnih kliničkih simptoma obilježenih korejom, psihičkim poremećajima, kognitivnim propadanjem i demencijom. Uzrok bolesti je povećan broj trinuklotidnih CAG ponavljanja na kromosomu 4 (4p16.3) koji kodira protein huntingtin (HTT). Specifičnog liječenja za bolest još uvijek nema te se terapija zasniva na ublažavanju simptoma u čemu glavnu ulogu imaju blokatori dopamina. Cilj rada bio u utvrditi učestalost i dužinu ponavljanja CAG tripleta kod pojedinaca sa sumnjom na Huntingtonovu bolest čiji su uzorci krvi testirani u KBC-u Zagreb u vremenskom periodu od siječnja 2003. do srpnja 2012. godine. Podaci su prikupljeni iz medicinske dokumentacije i obrađeni deskriptivnom statistikom. Analizom 486 uzoraka elekrtoforezom na gelu utvrđen je normalni broj ponavljanja tripleta CAG (do 26 ) u 303 uzorka (62%), intermedijarni broj ponavljanja tripleta CAG (27-35 ) utvrđen je kod 24 (5%) uzoraka, a ekspandirani aleli ( više od 36 CAG tripleta) bili su prisutni u 159 ( 33%) uzoraka.Huntington's disease is an autosomal dominant neurodegenerative disease that leads to characteristic clinical symptoms that manifest as chorea, psychiatric impairment, cognitive decline and dementia. The disease is caused by an increased number of CAG trinucleotide repeats on chromosome 4 (4p16.3) that encodes protein huntingtin (HTT). The selective therapy for Huntington's disease is still non-existent. Current therapy is symptomatic treatment where the dopamine blockers have turned out to be the most useful. The aim of the study has been to determine the frequency and the extension of CAG trinucleotide repeats in individuals suspected of having Huntington's disease (HD) whose blood samples were tested in UHC Zagreb in time period from January 2003 to July 2012. The data for this study has been gathered from medical documentation and analysed by descriptive statistics. Through the analysis of 486 blood samples by gel electrophoresis, the normal amount of CAG trinucleotide repeats (≤ 26 ) was found in 303 samples (62%), the intermediate number of CAG trinucleotide repeats (27-35) was found in 24 samples (5%), and the increased number CAG trinucleotide repeats was found to be present in 159 samples (33%)