, 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
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.