Genomic study finds undiagnosed DM1-associated expansions linked to cardiac disease

An observational study published in Brain analysed whole-genome sequencing data from Genomics England, UK Biobank and the All of Us Research Program to assess the frequency and clinical associations of DMPK repeat expansions underlying myotonic dystrophy type 1 (DM1). Researchers estimated repeat lengths using ExpansionHunter, classifying alleles with at least 50 CTG repeats as pathogenic. Linked health records were used to examine cardiac diagnoses and cataracts before age 55.

Among 985,026 participants, 645 carried pathogenic expansions (0.07%; approximately 1 in 1,527), two to five times higher than previous clinically based prevalence estimates. Expansions were detected across ancestry groups, although most occurred in participants of European ancestry. In UK Biobank, carriers had higher odds of any cardiac diagnosis (OR 2.06, 95% CI 1.58–2.67). The strongest association involved conduction abnormalities and atrial arrhythmias, including atrioventricular block, left bundle-branch block, atrial fibrillation and flutter (OR 4.86, 95% CI 3.38–6.79). Approximately one in ten carriers had cataracts diagnosed before age 55.

Most carriers had no previous DM1 diagnosis. The authors support including DMPK analysis in specified cardiac and ophthalmic diagnostic pathways. However, genetic expansion frequency should not be equated with clinically diagnosed disease prevalence. This observational analysis does not establish whether systematic testing improves outcomes; assessment here is limited to the abstract, without full-text methodological review.