Molecular analysis of the IT15 gene in patients with apparently 'sporadic' Huntington's disease

The diagnosis of Huntington's disease (HD) may be uncertain in patients without a positive family history, particularly when atypical clinical features are present. We examined the expanded trinucleotide (GAG) repeat sequence in the IT15 gene of 27 'sporadic' cases, classified as having clinically probable or clinically doubtful HD. An abnormal number of CAG repeats (42-85) were found in 14 patients. Mutation analysis confirmed the diagnosis in 63.6% of patients with clinically probable HD and in 43.7% of patients with clinically doubtful HD. DNA analysis allows an accurate diagnosis of apparently 'sporadic' HD patients and has important implications for genetic counselling.