Gene Analysis in Huntington Disease

ABSTRACT

BACKGROUND & OBJECTIVE: Huntington disease(HD) is clinically diagnosed by the triad of autosomal dominant inheritance, involuntary movements mainly chorea and dementia. The phenotype of HD is variable and other diseases can have same phenocopy. Therefore gene diagnosis of HD becomes essential for confirmatory diagnosis. Recent discovery of an expanded CAG trinucleotide repeat at the telomeric position of chromosome 4p made the gene diagnosis possible even in sporadic cases. We examined the length of CAG repeat in Huntington gene locus by PCR method in clinically diagnosed HB patients to make a confirmatory diagnosis. METHODS: Three patients with chorea, dementia and family history were tested. All laboratory tests including MRI had been normal so far. Genomic DNA was extracted from their WBC, and PCR was done on Huntington gene locus using primers modified from HD Collaboratory Group. Agarose gel electrophoresis to examine the rough degree of expansion, polyacrylamide gel electrophoresis to determine repeat length, and sequencing of the expanded allele were done. As a second step, three choreic patients without family history, one patient with tardive dyskinesia and one whole HD family were tested. RESULTS: Three choreic patients with family history showed expansion of CAG repeats in the amplified site. Two sporadic choreic patients, and one asymptomatic member in a HD family had increased CAG repeats. CONCLUSION: We confirmed expansion of CAG repeats in Huntington gene locus in clinically diagnosed HD. None of the patients had caudate atrophy, which has been considered an early finding. Sporadic choreic patients could be diagnosed as HD by gene study. Presymptomatic case was found in a family screening, and will need to be followed. Gene analysis offers a critical tool to make a confirmatory diagnosis of HD, and will be a powerful tool in genetic counseling.