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Huntington Disease: Molecular Diagnostics Approach
Murat Bastepe1,2,3, Winnie Xin1,4
1Neurogenetics DNA Diagnostic Laboratory, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Current Protocols in Human Genetics
|October 7, 2015
Summary
Huntington disease (HD) genetic testing detects CAG repeat expansions in the Huntingtin (HTT) gene for diagnosis and prediction. Protocols combine PCR and Southern blot for accurate repeat size measurement and interpretation.
Area of Science:
- Genetics
- Molecular Biology
- Neurology
Background:
- Huntington disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the Huntingtin (HTT) gene.
- Accurate detection of this expansion is crucial for diagnosis, disease prediction, and genetic counseling.
- Existing molecular testing methods require precise measurement of the CAG repeat size.
Purpose of the Study:
- To describe protocols for accurate molecular testing of Huntington disease.
- To detail the complementary use of polymerase chain reactions (PCR) and Southern blot hybridization for CAG repeat size measurement.
- To discuss interpretation of test results and indirect linkage analysis for prenatal testing.
Main Methods:
- Utilizing polymerase chain reactions (PCR) to amplify the CAG repeat region.
- Employing Southern blot hybridization for precise sizing of the expanded CAG trinucleotide repeat.
- Implementing indirect linkage analysis for prenatal diagnosis without revealing parental HD status.
Main Results:
- Established protocols accurately measure CAG trinucleotide repeat size in the HTT gene.
- Combined PCR and Southern blot provide reliable diagnostic and predictive information for Huntington disease.
- Indirect linkage analysis offers a method for prenatal testing while preserving privacy.
Conclusions:
- The described molecular testing protocols, combining PCR and Southern blot, are effective for Huntington disease diagnosis and prediction.
- Accurate CAG repeat size determination is essential for clinical management and genetic counseling.
- Indirect linkage analysis provides a valuable alternative for prenatal HD testing.
