Myotonic Dystrophy Type 1 (DM1): From the Genetics to Molecular Mechanisms

For a long time, the human genome was considered an intrinsically stable entity; however, it is currently known that our human genome contains many unstable elements consisting of tandem repeat elements, mainly Short tandem repeats (STR), also known as microsatellites or Simple sequence repeats (SSR) (Ellegren, 2000). These sequences involve a repetitive unit of 1-6 bp, forming series with lengths from two to several thousand nucleotides. STR are widely found in proand eukaryotes, including humans. They appear scattered more or less evenly throughout the human genome, accounting for ca. 3% of the entire genome (Sharma et al., 2007). STR are polymorphic but stable in general population; however, repeats can become unstable during DNA replication, resulting in mitotic or meiotic contractions or expansions. STR instability is an important and unique form of mutation that is linked to >40 neurological, neurodegenerative, and neuromuscular disorders (Pearson et al., 2005). In particular, abnormal expansion of trinucleotide repeats (CTG)n, (CGG)n, (CCG)n, (GAA)n, and (CAG)n have been associated with different diseases such as fragile X syndrome, Huntington disease (HD), Dentatorubral-pallidoluysian atrophy (DRPLA), Friedreich ataxia (FA), diverse Spinocerebellar ataxias (SCA), and Myotonic dystrophy type 1 (DM1).