Myotonic Dystrophy 2 (CNBP)
| Dred_ID | RD00051 |
| OMIM ID | 602668 |
| Disease name | Myotonic Dystrophy 2 |
| Alternative names | Proximal Myotonic Myopathy Myotonic Dystrophy Type 2 Ricker Syndrome Promm Dystrophia Myotonica Type 2 |
| Category | Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Reproductive diseases, Endocrine diseases, Muscle diseases |
| Phenotype | NIH Rare Diseases: Myotonic dystrophy type 2, one of the two types of myotonic dystrophy, is an inherited muscular dystrophy that affects the muscles and other body systems (e.g., heart, eyes, and pancreas). It is characterized by prolonged muscle tensing (myotonia) as well as muscle weakness, pain, and stiffness. Signs and symptoms usually develop during a person's twenties or thirties. Muscles in the neck, fingers, elbows, and hips are typically affected; facial and ankle muscles are less commonly involved. The severity of myotonic dystrophy type 2 varies widely among affected people, even among family members. It is inherited in an autosomal dominant pattern and is caused by mutations in the CNBP gene. Treatment is based on each person's specific signs and symptoms.
OMIM: Myotonic dystrophy (DM) is a multisystem disorder and the most common form of muscular dystrophy in adults. Individuals with DM2 have muscle pain and stiffness, progressive muscle weakness, myotonia, male hypogonadism, cardiac arrhythmias, diabetes, and early cataracts. Other features may include cognitive dysfunction, hypersomnia, tremor, and hearing loss (summary by Heatwole et al., 2011). See also myotonic dystrophy-1 (DM1; 160900), caused by an expanded CTG repeat in the dystrophia myotonica protein kinase gene (DMPK; 605377) on 19q13. Although originally reported as 2 disorders, myotonic dystrophy-2 and proximal myotonic myopathy are now referred to collectively as DM2 (Udd et al., 2003). (602668) |
| Miscellaneouse | OMIM: variable age of onset (range 13 to 67 years, median 48 years) no congenital form pathogenic alleles contain 75-11,000 repeats normal alleles contain up to 30 repeats repeat tracts may expand as patient ages (somatic instability) smaller repeat lengths in younger generations (reverse anticipation) see myotonic dystonia 1 (dm1, ) for a disorder with a similar phenotype |
| Prevalence | 1-9/100000 (Germany),1-9/100000 (Europe),1-5/10000 (Finland),1-9/1000000 (United Kingdom) [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | CNBP |
| Alias symbols | DM2; ZNF9; CNBP1; PROMM; RNF163; ZCCHC22 |
| Gene name | CCHC-type zinc finger nucleic acid binding protein |
| Gene map locus | 3q21.3; chr3:129,167,827-129,183,922(-) |
| Ensembl Gene ID | ENSG00000169714 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | This gene encodes a nucleic-acid binding protein with seven zinc-finger domains. The protein has a preference for binding single stranded DNA and RNA. The protein functions in cap-independent translation of ornithine decarboxylase mRNA, and may also function in sterol-mediated transcriptional regulation. A CCTG expansion from <30 repeats to 75-11000 repeats in the first intron of this gene results in myotonic dystrophy type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2016] |
| Repeat unit | CCTG |
| Normal repeat copies | 11-30 |
| Pathogenic repeat copies | ≥75 |
| Gene | CNBP |
| Repeat location | intron |
| Chromosome locus | chr3:129172622-129172656 (-) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | Lim et al. (2008) demonstrated that the expanded polyglutamine tract of ATXN1 differentially affects the function of the host protein in the context of different endogenous protein complexes. Polyglutamine expansion in ATXN1 favors the formation of a particular protein complex containing RBM17 (606935), contributing to SCA1 neuropathology by means of a gain-of-function mechanism. Concomitantly, polyglutamine expansion attenuates the formation and function of another protein complex containing ATXN1 and capicua, contributing to SCA1 through a partial loss-of-function mechanism. Lim et al. (2008) concluded that their model provides mechanistic insight into the molecular pathogenesis of SCA1 as well as other polyglutamine diseases.
Jain and Vale (2017) showed that repeat expansions create templates for multivalent basepairing, which causes purified RNA to undergo a sol-gel transition in vitro at a similar critical repeat number as observed in Huntington disease, spinocerebellar ataxia, myotonic dystrophy, and FTDALS1 (105550). In human cells, RNA foci form by phase separation of the repeat-containing RNA and can be dissolved by agents that disrupt RNA gelation in vitro. Jain and Vale (2017) concluded that, analogous to protein aggregation disorders, their results suggested that the sequence-specific gelation of RNAs could be a contributing factor to neurologic disease. |
| Pathway annotation | Reactome, KEGG |
| PMID | 22706481 |
| Authors | Giagnacovo M, Malatesta M, Cardani R, Meola G, Pellicciari C. |
| Title | Nuclear ribonucleoprotein-containing foci increase in size in non-dividing cells from patients with myotonic dystrophy type 2 |
| Journal | Histochem Cell Biol. 138:699–707 |
| Year | 2012 |
| PMID | 20100232 |
| Authors | Kirzinger L, Schmidt A, Kornblum C, Schneider-Gold C, Kress W, Schoser B. |
| Title | Side effects of anesthesia in DM2 as compared to DM1: a comparative retrospective study |
| Journal | Eur J Neurol. 17:842–5 |
| Year | 2010 |