Background: Uncertainty in diagnosing Huntington's disease (HD) may occur in the absence of a family history or typical movement disorders. HD is characterized by a progressive disturbance of typical movement disorders (i.e., chorea, athetosis), psychiatric symptoms (i.e., depression, insomnia, anxiety, suspiciousness), and cognitive deterioration, in the absence of a dominant family history of similar disorders. Often, some of these symptoms are missing, which makes the diagnosis difficult. In recent years molecular testing has become the gold standard for diagnosing HD. Diagnostic accuracy for HD on genetic screening of patients and their families is important. We evaluated a polymerase chain reaction (PCR) technique for the detection of CAG trinucleotide repeats in the Huntington IT15 gene on chromosome 4 for the diagnosis of HD.
Methods: A segment of the Huntington gene was amplified by PCR using the primers HD-1 and HD-3 flanking the CAG repeat sequence. Genomic PCR was performed on DNA extracted from the peripheral leukocytes of 12 patients from three unrelated families. One family had no documented history of movement or mental disorders, while the other two did. These two, therefore, required pre-symptomatic testing and exclusion of diagnosis in a seemingly symptomatic case.
Results: We successfully identified four subjects with expansion of CAG trinucleotide repeats in Huntington gene IT15 on chromosome 4. Movement disorder was present in three of these subjects. One was the sister of subject 4, who was asymptomatic. A sister of subject 9 was ruled out from having HD by PCR despite having depression symptoms, which are frequently seen in HD patients.
Conclusions: Genetic testing is of prime importance in the establishment of an accurate diagnosis of Huntington's disease, especially in "sporadic" cases and presymptomatic family members, and for the exclusion of HD in family members with equivocal symptoms.