Chapter 15, Problem 2CS

CASE STUDY|A mysterious muscular dystrophy

A man in his early 30s suddenly developed weakness in his hands and neck, followed a few weeks later by burning muscle pain–all symptoms of late-onset muscular dystrophy. His internist ordered genetic tests to determine whether he had one of the inherited muscular dystrophies, focusing on Becker muscular dystrophy, myotonic dystrophy Type I, and myotonic dystrophy Type II. These tests were designed to detect mutations in the related dystrophin, DMPK, and ZNF9 genes. The testing ruled out Becker muscular dystrophy. While awaiting the results of the DMPK and ZNF9 gene tests, the internist explained that the possible mutations were due to expanded tri- and tetranucleotide repeats, but not in the protein-coding portion of the genes. She went on to say that the resulting disorders were due not to changes in the encoded proteins, which appear to be normal, but instead to altered RNA splicing patterns, whereby the RNA splicing remnants containing the nucleotide repeats disrupt normal splicing of the transcripts of other genes. This discussion raises several interesting questions about the diagnosis and genetic basis of the disorders.

What role might the expanded tri- and tetranucleotide repeats play in the altered splicing?