Myotonic dystrophy: will the real gene please step forward!
- PMID: 8875246
- DOI: 10.1093/hmg/5.supplement_1.1417
Myotonic dystrophy: will the real gene please step forward!
Abstract
The mutation underlying myotonic dystrophy (DM) was identified at the end of 1991 amidst great rejoicing from the patients supporting the research and, not least, from those who spent so long searching for it. Subsequently, the molecular genetic phenomena associated with DM have been clearly explained by the transmission behaviour of the expanding repeat, which remains the only mutation that has been described in patients. We understand the molecular basis of anticipation, why the severe congenital form is almost exclusively transmitted by affected mothers and we have widely accepted models of the population genetics of DM. Yet, despite all these clearly explained molecular events, we appear to be hardly any closer to understanding the molecular pathology of DM than when the mutation was first identified. To understand the reason for this, we have to look in detail at the mutation itself, and in particular at the locus and its complex nuances. In doing so, we begin to realise that DM is unique amongst the Mendelianly inherited disorders, in that the mutation, because of its location in a very gene-rich region of the genome, probably simultaneously renders several genes dysfunctional. The somatic heterogeneity of the repeat, coupled with the involvement of several genes, accounts for the pleiotropy observed in the phenotype. Added to this complexity is the uncertainty of the level at which gene dysfunction or gain of function is occurring. It is possibly at the level of DNA/chromatin structure and/or RNA regulation/processing, and all of these pathways may, in different tissues, contribute to the final phenotype.
Similar articles
-
Effect of the myotonic dystrophy (DM) mutation on mRNA levels of the DM gene.Nat Genet. 1993 Jul;4(3):233-8. doi: 10.1038/ng0793-233. Nat Genet. 1993. PMID: 8358430
-
Correlation between CTG trinucleotide repeat length and frequency of severe congenital myotonic dystrophy.Nat Genet. 1992 Jun;1(3):192-5. doi: 10.1038/ng0692-192. Nat Genet. 1992. PMID: 1303233
-
[DNA diagnosis in myotonic dystrophy].Hokkaido Igaku Zasshi. 1996 Jan;71(1):3-8. Hokkaido Igaku Zasshi. 1996. PMID: 8727368 Review. Japanese.
-
Structure and genomic sequence of the myotonic dystrophy (DM kinase) gene.Hum Mol Genet. 1993 Mar;2(3):299-304. doi: 10.1093/hmg/2.3.299. Hum Mol Genet. 1993. PMID: 8499920
-
[Molecular genetics of myotonic dystrophy--population genetics of the CTG repeat expansion of the MTPK gene].Nihon Rinsho. 1997 Dec;55(12):3205-9. Nihon Rinsho. 1997. PMID: 9436437 Review. Japanese.
Cited by
-
Repeat expansion disease: progress and puzzles in disease pathogenesis.Nat Rev Genet. 2010 Apr;11(4):247-58. doi: 10.1038/nrg2748. Nat Rev Genet. 2010. PMID: 20177426 Free PMC article. Review.
-
Long CAG/CTG repeats in mice.Mamm Genome. 1998 May;9(5):392-3. doi: 10.1007/s003359900778. Mamm Genome. 1998. PMID: 9545500 No abstract available.
-
Cancer and Myotonic Dystrophy.J Clin Med. 2023 Mar 1;12(5):1939. doi: 10.3390/jcm12051939. J Clin Med. 2023. PMID: 36902726 Free PMC article. Review.
-
Polymorphisms of the glucocorticoid receptor gene in laboratory and wild rats: steroid binding properties of trinucleotide CAG repeat length variants.Mamm Genome. 1998 Mar;9(3):198-203. doi: 10.1007/s003359900725. Mamm Genome. 1998. PMID: 9501302
-
RNA surveillance: molecular approaches in transcript quality control and their implications in clinical diseases.Mol Med. 2010 Jan-Feb;16(1-2):53-68. doi: 10.2119/molmed.2009.00026. Epub 2009 Oct 7. Mol Med. 2010. PMID: 19829759 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
