Improving the Prognosis and Genetic Counseling in DM1 Patients

In this talk, Dr. Stephanie Tome describes using PacBio Single Molecule, Real-Time (SMRT) Sequencing to precisely measure large CTG repeat size and identify sequence interruptions of expanded allele to understand clinical and genetic variability in DM1 patients, sequencing several DM1 patients with CTG repeat expansion ranging from 130 to > 1000 CTG repeats on the Sequel I and II Systems from amplicons. She obtained more than 77% full DM1 reads per sample, with >70% of the reads from expanded alleles. The data includes long reads in the expected size range for all samples, including DM1 patients with more than 1000 CTG repeats. She concludes that SMRT Sequencing is very promising in its ability to sequence large triplet repeat expansions, to identify CTG repeat interruptions and to estimate somatic mosaicism in DM1 patients. In parallel, she has developed amplification free-targeted sequencing in DM1 to avoid the limitations due to PCR amplification. Both of these methods can significantly improve the prognosis and counseling offered to patients.