TY - CHAP
T1 - Myotonic Dystrophy Type 2
T2 - Clinical and Genetic Aspects
AU - Krahe, Ralf
AU - Bachinski, Linda L.
AU - Udd, Bjarne
N1 - Funding Information:
R. K. and L. L. B. thank the members of the Krahe laboratory for valuable discussions and Keith A. Baggerly and E. Lin for assistance with bioinformatics analyses of DM gene expression profiling data. We thank the European Neuro-Muscular Centre (ENMC) for their continued support of the International Working Group on DM2/PROMM and Other Myotonic Dystrophies and the numerous, participating collaborators of the group. R. K. was supported by grants from the NIH (AR48171); B. U. was supported by Medicinska understödsföreningen Liv och Hälsa r.f., the Tampere University Hospital Research Funds, and the Folkhälsan Institute of Genetics.
Publisher Copyright:
© 2006 Elsevier Inc. All rights reserved.
PY - 2006/7/11
Y1 - 2006/7/11
N2 - This chapter discusses clinical and genetic aspects of myotonic dystrophy type 2 (DM2). The frequent major complaints and signs, or core features of DM2 are: proximal muscle weakness, muscle pain and/or stiffness, cataracts, myotonia, tremor, cardiac disturbance, endocrinological abnormalities, and elevated ?-glutamyl transferase (?-GT). The mutant DM2 repeat is located within intron 1 of the ZNF9 gene in chromosome 3q21.3 and is composed of a complex motif with several polymorphic elements. The developing paradigm is that DM is an RNA disease, mediated by the mutant expansion of normally polymorphic microsatellite repeats with a (CTG)n-like repeat motif. Transcription of the mutant repeats into (CUG)n/(CCUG)n. RNA is both necessary and sufficient to cause disease. Mutant RNA species accumulate in ribonuclear inclusions and interfere with proper RNA splicing, transcription, and/or translation of a number of effecter genes, resulting in the pleiotropic phenotype characteristic of this disease. This interference may be due, in part, to sequestration of various proteins involved in cellular processes.
AB - This chapter discusses clinical and genetic aspects of myotonic dystrophy type 2 (DM2). The frequent major complaints and signs, or core features of DM2 are: proximal muscle weakness, muscle pain and/or stiffness, cataracts, myotonia, tremor, cardiac disturbance, endocrinological abnormalities, and elevated ?-glutamyl transferase (?-GT). The mutant DM2 repeat is located within intron 1 of the ZNF9 gene in chromosome 3q21.3 and is composed of a complex motif with several polymorphic elements. The developing paradigm is that DM is an RNA disease, mediated by the mutant expansion of normally polymorphic microsatellite repeats with a (CTG)n-like repeat motif. Transcription of the mutant repeats into (CUG)n/(CCUG)n. RNA is both necessary and sufficient to cause disease. Mutant RNA species accumulate in ribonuclear inclusions and interfere with proper RNA splicing, transcription, and/or translation of a number of effecter genes, resulting in the pleiotropic phenotype characteristic of this disease. This interference may be due, in part, to sequestration of various proteins involved in cellular processes.
UR - http://www.scopus.com/inward/record.url?scp=62549109350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=62549109350&partnerID=8YFLogxK
U2 - 10.1016/B978-012369462-1/50009-0
DO - 10.1016/B978-012369462-1/50009-0
M3 - Chapter
AN - SCOPUS:62549109350
SN - 9780123694621
SP - 131
EP - 150
BT - Genetic Instabilities and Neurological Diseases
PB - Elsevier
ER -