Genetic determinants of disease severity in the myotonic dystrophy type 1 OPTIMISTIC cohort.

ABSTRACT:

Objective

To evaluate the role of genetic variation at the DMPK locus on symptomatic diversity in 250 adult, ambulant patients with myotonic dystrophy type 1 (DM1) recruited to the Observational Prolonged Trial in Myotonic Dystrophy Type 1 to Improve Quality of Life-Standards, a Target Identification Collaboration (OPTIMISTIC) clinical trial.

Methods

We used small pool PCR to correct age at sampling biases and estimate the progenitor allele CTG repeat length and somatic mutational dynamics, and AciI digests and repeat primed PCR to test for the presence of variant repeats.

Results

We confirmed disease severity is driven by progenitor allele length, is further modified by age, and, in some cases, sex, and that patients in whom the CTG repeat expands more rapidly

SUBMITTER: Cumming SA 

PROVIDER: S-EPMC6745735 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature