Molecular genetics of congenital myotonic dystrophy

[摘要] Myotonic Dystrophy type 1 (DM1) is a neuromuscular disease showing strong genetic anticipation, and is caused by the expansion of a CTG repeat tract in the 3'-UTR of the DMPK gene. Congenital Myotonic Dystrophy (CDM1) represents the most severe form of the disease, with prenatal onset, symptoms distinct from adult onset DM1, and a high rate of perinatal mortality. CDM1 is usually associated with very large CTG expansions, but this correlation is not absolute and cannot explain the distinct clinical features and the strong bias for maternal transmission. This review focuses upon the molecular and epigenetic factors that modulate disease severity and might be responsible for CDM1. Changes in the epigenetic status of the DM1 locus and in gene expression have recently been observed. Increasing evidence supports a role of a CTCF binding motif as a cis-element, upstream of the DMPK CTG tract, whereby CpG methylation of this site regulates the interaction of the insulator protein CTCF as a modulating trans-factor responsible for the inheritance and expression of CDM1.

[发布日期] 2019-12-01

[关键词] Myotonic Dystrophy type 1;Congenital Myotonic Dystrophy;Repeat instability;Parent-of-origin effect;DNA methylation;Epigenetics