MBNL1 overexpression is not sufficient to rescue the phenotypes in a mouse model of RNA toxicity.

Myotonic dystrophy type 1 (DM1) is caused by an expanded (CTG)n tract in the 3'UTR of the DM protein kinase (DMPK) gene. The RNA transcripts produced from the expanded allele sequester or alter the function of RNA-binding proteins (MBNL1, CUGBP1, etc.).

Disease Phenotypes in a Mouse Model of RNA Toxicity Are Independent of Protein Kinase Cα and Protein Kinase Cβ.

Myotonic dystrophy type 1(DM1) is the prototype for diseases caused by RNA toxicity. RNAs from the mutant allele contain an expanded (CUG)n tract within the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The toxic RNAs affect the function of RNA binding proteins leading to sequestration of muscleblind-like (MBNL) proteins and increased levels of CELF1 (CUGBP, Elav-like family member 1).

Chronotropic incompetence precedes silent pulmonary embolism.

A patient with recurrent pulmonary emboli collected heart rate data during exercise, which provided important premorbid clues to changes in cardiopulmonary exercise tolerance coincident with accrual of thrombus in the central circulation. On both occasions, chronotropic incompetence (CI) preceded the pulmonary emboli events. When patients with programmed exercise goals notice CI, they should seek professional guidance.