Background The presence of 36 or more CAG trinucleotide repeats in the huntingtin gene essentially ensures the development of Huntington's disease (HD). However, there is emerging evidence that clinical and neuro-pathological manifestations of HD may occur in individuals with intermediate length CAG repeats (27–35 CAG repeats).
Objectives To define the clinical characteristics of individuals who possess CAG repeat lengths in this range.
Methods Data from the Euro-HD REGISTRY from two centres in Spain were analysed. We included individuals with intermediate (27–35) CAG repeats. The motor, cognitive and behavioural scores of the Unified Huntington's Disease Rating Scale were analysed.
Results Of 176 individuals affected by HD or with a family history of HD who were genotyped, eight individuals (4.5%) had their larger CAG repeat in the intermediate range (50% males). In two patients, 33% of the intermediate group of patients, the Unified Huntington's Disease Rating Scale motor score ranged from 22 to 6, cognitive score from 242 to 76 and the behaviour score from 16 to 1.
Conclusions Our findings of motor, cognitive and behavioural abnormalities in some individuals with intermediate CAG repeats suggest the presence of subtle, but relevant, disease manifestations. These results have important implications for the pathogenesis of the disease and genetic counselling.
- Intermediate repeats