Abstract:
Huntington’s Disease (HD) is a progressive and fatal neurodegenerative disorder that follows an autosomal dominant pattern of inheritance. The clinical symptoms of HD are disability in motor control, cognitive dysfunction and psychiatric disturbances. HD is an adult-onset disease, the onset occurs between the ages of 35 and 50 years. The causative mutation for HD was identified as the expansion of polymorphic CAG repeats in the first exon of the HD gene. It is well-established that there is a strong inverse correlation between the age of onset and expanded CAG repeat length in HD. However, the expanded CAG repeat number in the first exon of the HD gene explains about 42-73 per cent of the variance in the age of onset of the disease. The remaining variation in the age of onset is due to the combination of both environmental and genetic factors beyond the HD gene. An extensive research is conducted on the identification of possible modifiers of age of onset in HD and variations in several genes were found to have modifier effects. It is essential to demonstrate the presence or absence of the modifier effects of previously studied genes in different populations. The aims of this study are to i) investigate the molecular basis of HD in Turkish HD patients, ii) analyze the correlation between the age of onset and CAG repeat genotypes in the HD gene and iii) study the statistical significance of modifier effects of five polymorphisms in three different genes, encoding glutamate receptors, on the age of onset in HD. 108 Turkish HD patients, including an extended kindred, were studied in the framework of this thesis. Our findings did not demonstrate any significant association between the polymorphisms studied and the age of onset in HD. This result does not rule out the roles of these genes in HD. In the literature, there are several contradictions for the polymorphisms studied in this thesis. Analysis of these polymorphisms in a larger study population is apparently needed. We believe that the present study is a first step towards this direction.
