[12], some patterns have emerged with respect to disease onset and clinical features when homozygous
trinucleotide repeat expansion is compared to those with compound heterozygosity.
A PCR method for accurate assessment of
trinucleotide repeat expansion in Huntington disease.
POOLED
TRINUCLEOTIDE REPEAT EXPANSION SIZE DETERMINATION
A novel PCR-based approach for the detection of the Huntington disease associated
trinucleotide repeat expansion. Hum Mutat 1999;13: 232-6.
The abbreviated process likely will be sufficient for all mutations except
trinucleotide repeat expansion mutations, which would require special handling as discussed above.
After a 10-year struggle, during which fundamental strategies of positional cloning were developed, the causative mutation, a CAG
trinucleotide repeat expansion, was identified (4).
SCA type 3, also known as Machado-Joseph disease, is the most frequent form worldwide, followed by SCA types 1, 2, 6, and 7.5 This group of SCAs (1, 2, 3, 6, and 7) is caused by CAG
trinucleotide repeat expansions that result in elongated polyglutamine tracts within the coding region of the associated genes: SCA1, ATXN1; SCA2, ATXN2; SCA3, ATXN3; SCA6, CACNA1A; and SCA7, ATXN7.
Third, it is anticipated that long reads produced by this technology will greatly enhance the ability to address the aforementioned challenging genomic scenarios like copy number variants (CNVs) and
trinucleotide repeat expansions as well as provide haplotype information and identify alternatively spliced mRNAs.
The Southern blotting technique is invaluable for detecting large fragments, in diseases such as fragile X and myotonic dystrophy, in which the disease-causing
trinucleotide repeat expansions are too large to be successfully generated by polymerase chain reaction.
Most importantly, some of the neurodegenerative diseases under investigation are caused by
trinucleotide repeat expansions, and evidence of successful ASO therapeutic strategies for this type of disorder is rapidly accumulating.
