Abstract
Introduction: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, caused by abnormal expansion of the CAG trinucleotide in the HTT gene. The clinical profile includes a triad of motor, cognitive and psychiatric alterations. The number of CAG repeats or CAG genotype(n) significantly impacts the clinical profile. The objective of this study is to describe the clinical profile of HD and its association with the CAG(n) genotype in a sample of patients from southeastern Mexico.
Materials and methods: 25 patients with clinical diagnosis of HD confirmed by genetic testing and having complete medical record, were included. The clinical profile was defined covering motor, cognitive and behavioral/psychiatric domains. The genotype (CAG)n was determined by PCR and Sanger sequencing. Descriptive analyzes and Pearson correlation coefficient were performed.
Results: 96% presented motor symptoms, 84% cognitive and 76% psychiatric symptoms. Choreic movements, executive dysfunction and personality changes were the prevalent manifestations in each dimension. The range of CAG(n) was 12 to 28 for normal alleles and 41 to 77 for mutated alleles. The mean CAG(n) in normal alleles was significantly higher in women (p=0.017). An inverse relationship was found between CAG(n) and age at onset of symptoms (p=0.000083), with no significant association with HD severity (p>0.05).
Discussion: The number of motor, cognitive, and psychiatric symptoms were distributed independently of CAG(n), suggesting no association with the severity of HD; whereas the inverse association between higher CAG(n) and early age of onset of signs and symptoms was replicated.
Conclusions: The clinical profile predominantly consists of the triad of choreic movements, executive dysfunction, and personality changes. Sixty-four percent of the mutated alleles were maternally transmitted. The inverse association between CAG(n) and age at onset of HD was confirmed, with no relation to disease severity.
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