The June issue of Current Opinion in Genetics and Development is focused on the topic "Molecular and Genetic Bases of Disease." Four outstanding review articles in the issue have direct relevance to myotonic dystrophy (DM) and are currently available online.
The first article (by Drs. Nan Zhang and Tetsuo Ashizawa) reviews the formation of RNA foci in microsatellite expansion disorders, how RNA binding proteins participate in toxic RNA gain of function, and how transcriptional and RNA processing/transport may ensue.
The second article (by Drs. Kevin Yum, Eric Wang, and Auinash Kalsotra) discusses mechanisms underlying repeat expansion, diagnostic approaches to determining repeat length, and how DM repeat length relates to disease onset, progression and severity.
The third article (by Drs. John Cleary and Laura Ranum) reviews basic mechanisms of repeat-associated non-ATG (RAN) translation and how RAN proteins may enter into the pathogenesis of microsatellite expansion disorders, including DM.
The fourth article (by Drs. Charles Thornton, Eric Wang and Ellie Carrell) focuses on the latest molecular strategies being used in the development of candidate therapies for DM, reviewing approaches targeted at transcriptional silencing, post-transcriptional silencing, inhibition of interactions between MBNL and toxic RNA, and pathways downstream of RNA toxicity.
Taken together, this is a compelling series of review articles, of benefit to basic, translational, and clinical scientists of all levels working on DM.
RNA Toxicity and Foci Formation in Microsatellite Expansion Diseases
Zhang N, Ashizawa T.
Curr Opin Genet Dev. 2017 Feb 13;44:17-29. doi: 10.1016/j.gde.2017.01.005. [Epub ahead of print]
Myotonic Dystrophy: Disease Repeat Range, Penetrance, Age of Onset, and Relationship between Repeat Size and Phenotypes
Yum K, Wang ET, Kalsotra A.
Curr Opin Genet Dev. 2017 Feb 14;44:30-37. doi: 10.1016/j.gde.2017.01.007. [Epub ahead of print]
New Developments in RAN Translation: Insights from Multiple Diseases
Cleary JD, Ranum LP.
Curr Opin Genet Dev. 2017 Mar 30;44:125-134. doi: 10.1016/j.gde.2017.03.006. [Epub ahead of print]
Myotonic Dystrophy: Approach to Therapy
Thornton CA, Wang E, Carrell EM.
Curr Opin Genet Dev. 2017 Apr 1;44:135-140. doi: 10.1016/j.gde.2017.03.007. [Epub ahead of print]