An Unstable Triplet Repeat in a Gene Related to Myotonic Muscular Dystrophy

TLDR

The DM locus contains a GC‑rich triplet repeat within a gene homologous to protein kinases, termed myotonin‑protein kinase. The authors employed synthetic GC‑rich triplet oligonucleotides in a scanning assay to locate unstable sequences at the DM locus. A highly polymorphic GCT repeat was identified as unstable, with expanded repeats in DM patients and maternal inheritance of the unstable allele, suggesting that DM results from triplet amplification similar to fragile X syndrome.

Abstract

Synthetic oligonucleotides containing GC-rich triplet sequences were used in a scanning strategy to identify unstable genetic sequences at the myotonic dystrophy (DM) locus. A highly polymorphic GCT repeat was identified and found to be unstable, with an increased number of repeats occurring in DM patients. In the case of severe congenital DM, the paternal triplet allele was inherited unaltered while the maternal, DM-associated allele was unstable. These studies suggest that the mutational mechanism leading to DM is triplet amplification, similar to that occurring in the fragile X syndrome. The triplet repeat sequence is within a gene (to be referred to as myotonin-protein kinase), which has a sequence similar to protein kinases.