Myotonic Dystrophy Type 2 Caused by a CCTG Expansion in Intron 1 of ZNF9

@article{Liquori2001MyotonicDT,
  title={Myotonic Dystrophy Type 2 Caused by a CCTG Expansion in Intron 1 of ZNF9},
  author={Christina L. Liquori and Kenneth Ricker and Melinda L. Moseley and Jennifer F. Jacobsen and Wolfram Kress and S. L. Naylor and John W. Day and Laura P. W. Ranum},
  journal={Science},
  year={2001},
  volume={293},
  pages={864 - 867}
}
Myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, can be caused by a mutation on either chromosome 19q13 (DM1) or 3q21 (DM2/PROMM). DM1 is caused by a CTG expansion in the 3′ untranslated region of the dystrophia myotonica–protein kinase gene (DMPK). Several mechanisms have been invoked to explain how this mutation, which does not alter the protein-coding portion of a gene, causes the specific constellation of clinical features characteristic of DM. We now report… 
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1,175 Citations

Pathogenic mechanisms of myotonic dystrophy.

The RNA gain-of-function disease mechanism, the important roles of MBNL1 and CUGBP1 in DM1, and the relevance to other RNA dominant disorders are focused on.

Myotonic dystrophy: Clinical and molecular parallels between myotonic dystrophy type 1 and type 2

  • L. RanumJ. Day
  • Medicine
    Current neurology and neuroscience reports
  • 2002
The recent discovery that DM2 is caused by an untranslated CCTG expansion, along with other discoveries on DM1 pathogenesis, indicate that the clinical features common to both diseases are caused by a gain of function RNA mechanism in which the CUG and CCUG repeats alter cellular function, including alternative splicing of various genes.

SPLICING ABNORMALITIES IN MYOTONIC DYSTROPHIES

An overview of the DM splicing mis-regulation will be presented, with focus on mis- regulation of the BIN1 mRNA, which plays an important role in tubular invaginations of the plasma membrane and is required for biogenesis of T-tubules, which are specialized membrane structures essential for excitation-contraction coupling.

RNA-mediated neuromuscular disorders.

Evidence that similar mechanisms may play a role in a growing number of dominant noncoding expansion disorders, including fragile X tremor ataxia syndrome (FXTAS), spinocerebellarAtaxia type 8 (SCA8), SCA10, SCA12, and Huntington's disease-like 2 (HDL2) is discussed.

Myotonic dystrophy: emerging mechanisms for DM1 and DM2.

Myotonic dystrophy: RNA pathogenesis comes into focus.

The recent discovery that myotonic dystrophy type 2 (DM2) is caused by an untranslated CCTG expansion, along with other discoveries on DM1 pathogenesis, indicate that the clinical features common to both diseases are caused by a gain-of-function RNA mechanism in which the CUG and CCUG repeats alter cellular function, including alternative splicing of various genes.

[Myotonic dystrophy - a new insight into a well-known disease].

Myotonic dystrophy type 2 and related myotonic disorders

The detailed clinical, laboratory and biomolecular tests to identify DM2 and related myotonic disorders are described and conventional molecular genetic methods used for diagnosis of DM1 are not helpful for DM2.

Molecular Diagnosis of Myotonic Dystrophy

The clinical phenotypes, genetic mutations causing the diseases, and the molecular diagnostic approaches and tools that are used to determine repeat sizes in DM1/2 are reviewed and discussed.

Myotonic dystrophy type 2 is rare in the Japanese population

The first case of DM2 was identified in an East-Asian population, in a Japanese patient with a disease haplotype distinct from that shared among Caucasians, indicating that DM2 exists in non-Caucasian populations and that there may have been separate founders.
...

References

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