caa a22 4500 397575742 CHVBK 20180308164855.0 cr unu---uuuuu 161202e199609 xx s 000 0 eng 10.1093/hmg/5.Supplement_1.1417 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.Supplement_1.1417 Myotonic dystrophy: will the real gene pleasestep forward! [Elektronische Daten] [Sarah Harris, Colin Moncrieff, Keith Johnson] 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. © 1996 Oxford University Press Harris Sarah Division of Molecular Genetics, IBLS, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow G11 6NU, UK aut Moncrieff Colin Division of Molecular Genetics, IBLS, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow G11 6NU, UK aut Johnson Keith Division of Molecular Genetics, IBLS, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow G11 6NU, UK aut Human Molecular Genetics Oxford University Press 5/Supplement_1(1996-09), 1417-1423 0964-6906 5:Supplement_1<1417 1996 5 hmg https://doi.org/10.1093/hmg/5.Supplement_1.1417 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.Supplement_1.1417 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Harris Sarah Division of Molecular Genetics, IBLS, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow G11 6NU, UK aut NATIONALLICENCE 700 1- Moncrieff Colin Division of Molecular Genetics, IBLS, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow G11 6NU, UK aut NATIONALLICENCE 700 1- Johnson Keith Division of Molecular Genetics, IBLS, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow G11 6NU, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/Supplement_1(1996-09), 1417-1423 0964-6906 5:Supplement_1<1417 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford