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Usefulness of molecular testing in Huntington's disease
1Department of Neurology, Cardinal Tien Hospital, Taipei Hsien, Taiwan, ROC.
Insights
Genetic testing using polymerase chain reaction (PCR) accurately diagnoses Huntington's disease (HD) by detecting CAG trinucleotide repeats. This method is crucial for diagnosing sporadic cases and confirming diagnoses in families.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Huntington's disease (HD) diagnosis can be challenging due to atypical presentations and lack of family history.
- Symptoms include movement disorders, psychiatric issues, and cognitive decline, but are often incomplete.
- Molecular testing, specifically genetic screening, is the gold standard for accurate HD diagnosis.
Purpose of the Study:
- To evaluate a polymerase chain reaction (PCR) technique for diagnosing Huntington's disease.
- To detect CAG trinucleotide repeats in the Huntington IT15 gene.
- To assess diagnostic accuracy in patients and families, including sporadic and presymptomatic cases.
Main Methods:
- Amplification of the Huntington gene segment containing the CAG repeat using PCR with specific primers (HD-1 and HD-3).
- Genomic PCR performed on DNA from peripheral leukocytes of 12 patients across three unrelated families.
- Inclusion of families with and without documented movement or mental disorders for comprehensive evaluation.
Main Results:
- Successfully identified four subjects with expanded CAG trinucleotide repeats in the Huntington IT15 gene.
- Three of the four identified subjects presented with movement disorders.
- PCR excluded HD in an asymptomatic sibling and in a patient with depression, highlighting its diagnostic utility.
Conclusions:
- Genetic testing via PCR is vital for accurate Huntington's disease diagnosis.
- Essential for diagnosing 'sporadic' cases and presymptomatic individuals.
- Crucial for excluding HD in family members with ambiguous symptoms.
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.