A new test may help to streamline genetic testing for Huntington's Disease by generating accurate results, avoiding unnecessary additional testing, and improving turnaround time. The test, which uses chimeric or triplet-repeat-primed PCR (TP PCR) methodology, yielded results that were 100% concordant with standard genotyping methods in an analysis of 246 samples. The high sensitivity and specificity of the test could reduce the number of false negative results and facilitate both diagnosis and prognosis by correctly sizing the genetic abnormality characteristic of the disease.
In this study, 246 samples that had been previously analyzed by other methods were tested with the new method (TP PCR). The samples included 14 DNA reference samples from the Coriell Cell Repositories, three samples from the College of American Pathologists 2002 Survey, and 229 samples from individuals tested at ARUP Laboratories for clinical purposes by standard technologies, explained lead investigator Elaine Lyon, PhD, Medical Director of Molecular Genetics, ARUP Laboratories and its Institute for Clinical and Experimental Pathology, and Department of Pathology, University of Utah, Salt Lake City, UT. Normal samples were included as well as those with a wide range of CAG repeats. The samples were blinded and analyzed.
The results, published in The Journal of Molecular Diagnostics
, showed that TP PCR correctly sized 240 of the 246 samples. All of the 100 samples in the normal and low risk groups were correctly sized. In the 146 samples of those known to be affected by Huntington's Disease (those with > 39 CAG repeats), the results for 140 correctly matched that found with other methods, whereas the number of CAG repeats differed by ±1 in 6 samples, a difference said by the authors to be within the precision of the method at higher repeat numbers. Up to 101 CAG repeats could be accurately sized with this test. Even samples that were found to be challenging to analyze with other methods could be assessed solely and accurately by TP PCR.
Another advantage of this new method is its ability to identify true homozygous normal samples, thus avoiding further testing.