>Gaceta Médica de México
>Year 2009, Issue 4
Magaña JJ, Leyva-García N, Cisneros B
Patogénesis de la distrofia miotónica tipo 1
Gac Med Mex 2009; 145 (4)
PDF: 204.98 Kb.
Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults, affecting 1/8000 individuals. DM1 is a dominant disorder characterized by multisystemic clinical features affecting skeletal muscle, heart and the nervous and endocrine systems. DM1 is caused by an expansion of CTG trinucleotide repeats within the 3’-untranslated region (3’-UTR) of the DMPK gene. This repeat is polymorphic in normal individuals with alleles ranging from 5 to 37 in length. Repeats exceeding a threshold of approximately 50 and reaching up to a number of 4,000 result in disease. This review offers a detailed description of the scientific findings that have allowed the establishment of the molecular basis of the DM1 in the muscle and nervous systems. Currently, it is known that mutant DM1 transcript accumulates in the nucleus of muscle and neuronal cells sequestering nuclear proteins, such as splicing regulators and transcription factors to form nuclear foci that are observed under inmunofluorescence techniques. This event disturbs the expression of several muscular and neuronal genes impairing cell differentiation, which may explain the multiple symptoms of the disease. Finally, the main findings towards the development of a gene therapy for DM1 are discussed.
||Myotonic dystrophy, trinucleotide repeats, molecular mechanism, DMPK, mRNA.
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>Gaceta Médica de México
>Year 2009, Issue 4