期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1772, 期 2, 页码 195-204出版社
ELSEVIER
DOI: 10.1016/j.bbadis.2006.05.013
关键词
myotonic dystrophy; repeat expansion; DMPK; ZNF9; MBNL; CUG-BP
资金
- NIAMS NIH HHS [AR050741, AR4203] Funding Source: Medline
Myotonic dystrophy (DM) is a complex multisystemic disorder linked to two different genetic loci. Myotonic dystrophy type 1 (DM1) is caused by an expansion of a CTG repeat located in the 3' untranslated region (UTR) of DMPK (myotonic dystrophy protein kinase) on chromosome 19q13.3. Myotonic dystrophy type 2 (DM2) is caused by an unstable CCTG repeat in intron 1 of ZNF9 (zinc finger protein 9) on chromosome 3q21. Therefore, both DM I and DM2 are caused by a repeat expansion in a region transcribed into RNA but not translated into protein. The discovery that these two distinct mutations cause largely similar clinical syndromes put emphasis on the molecular properties they have in common, namely, RNA transcripts containing expanded, non-translated repeats. The mutant RNA transcripts of DM1 and DM2 aberrantly affect the splicing of the same target RNAs, such as chloride channel 1 (CIC-1) and insulin receptor (INSR), resulting in their shared myotonia and insulin resistance. Whether the entire disease pathology of DM1 and DM2 is caused by interference in RNA processing remains to be seen. This review focuses on the molecular significance of the similarities and differences between DM1 and DM2 in understanding the disease pathology of myotonic dystrophy. (c) 2006 Elsevier B.V. All rights reserved.
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