Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disorder associated with symptom variability. It is caused by an unstable expansion of CTG repeats that increases over generations and in tissues, up to 4000 CTGs. Clinical variability depends on the number of CTG repeats, CNG interruptions and somatic mosaicism.
Until now, the limitations of reference methods used in clinical and research laboratories have not allowed for simultaneous and accurate determination of any of these factors.
The REDs team at the Myology Institute developed a long-read sequencing method without amplification using CRISPR/Cas9 technology in DM1. The researchers showed that eliminating PCR amplification improves the accuracy of measuring the number of inherited repeats, triplet type, and somatic repeat variation, three key factors in DM1 severity and age of onset. For the first time, this innovative method allowed the identification of a CCG triplet-rich expansion in a DM1 family with an atypical clinical profile.
A promising method to overcome research and diagnostic gaps, targeted long-read sequencing without amplification may also be used for clinical and genetic counseling in DM1.
