Detection of CAG - repeat length in Huntington´s disease genetic testing


Iveta Boroňová (1), Jarmila Bernasovská (1), Ivan Bernasovský (2), Lucia Kulíková (1)


  1. Excellence Centre of Animal and Human Ecology, FHPV, University of Prešov, Prešov, Slovakia
  2. Institute of Romany Studies, University of Prešov, Prešov, Slovakia

Huntington´s disease (HD) is an autosomal dominant neurodegenerative disorder due to a trinucleotide (CAG) repeat expansion in IT 15. It most commonly presents in the third or fourth decade of life with slowly progressive cognitive, behavioral and motoric dysfunction. Gross pathology of HD is limited to the brain, with atrophy most prominent in the caudate, putamen, and cerebral cortex. Brain wight may be reduded by as much as 25-30% in advanced cases HD is spread worldwide and it is generally accepted that few mutational events account for the origin of the pathogenic CAG expansion in most populations. The prevalence rate of HD in the most of Europe is 5 cases per 100 000 individuals. HD gene encodes the protein huntingtin of 3136 amino acids.  The mutation of huntingtin produces an expanded stretch of glutamine (Gln) residues. The HD locus spans 180 kb and consists of 67 exons ranging in size from 48 bp to 341 bp with an average of 138 bp. The molecular basis of the disease is the expansion of the trinucleotide CAG in the first exon of the huntingtin gene in chromosome 4p16.3. Diagnosis of HD has been greatly simplified by the direct triplet repeat gene test. In the Prešov region (1998-2009) CAG repeat lenghts in the HD gene were tested in twelve patients with suspected diagnosis of HD. Genomic DNA was extracted from blood samples by standard extraction procedures.  PCR products were resolved on capillary electrophoresis with ABI technology. In seven affected patients clinical diagnosis of HD was confirmed by molecular-genetic methods. The sex ratio in the cases, in which the diagnosis of HD has been confirmed  was 4:3 in favor of female individuals. The mean age of patients in the time of diagnosis Huntington disease  was 44.1 and ranged from 28 to 62 years. This confirm the affirmation of onset of symptoms typically in the third and fourth decade of life. Mapping the occurance of HD in the Prešov region is a part of population-genetic analyses and monitoring of Prešov region population health status.

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