Disease relevance of Myotonic Dystrophy

• Targeted deletion of Dm15, the mouse orthologue of human DMPK, produced mice with a mild myopathy and cardiac conduction abnormalities, but without other features of myotonic dystrophy, such as myotonia and cataracts [1].
• Letter: Insulin action in myotonic dystrophy and acanthosis nigricans [2].
• The effect of an intrabrachial arterial insulin infusion (100 mu U/kg per min) on glucose uptake was determined in six cases of myotonic dystrophy, six normal subjects, and in seven disease control subjects with myotonia or wasting from other disorders [3].
• Previous studies of patients with myotonic dystrophy have demonstrated hyperinsulinism after glucose loading [3].
• These results demonstrate that DMPK dosage is a critical element modulating cardiac conduction integrity and conclusively link haploinsufficiency of DMPK with cardiac disease in myotonic dystrophy [4].

Psychiatry related information on Myotonic Dystrophy

• Loss of serotonin-containing neurons in the raphe of patients with myotonic dystrophy: a quantitative immunohistochemical study and relation to hypersomnia [5].
• We examined the autopsied brains of cases of 6 types of tauopathy: parkinsonism-dementia complex of Guam (PDC), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), Pick disease, Alzheimer disease (AD), and myotonic dystrophy together with Guamanian controls [6].
• Cerebral abnormalities in myotonic dystrophy. Cerebral blood flow, magnetic resonance imaging, and neuropsychological tests [7].
• Triplet repeat expansion has been related pathogenetically to six diseases: fragile X syndrome, fragile X E syndrome, spinobulbar muscular atrophy, myotonic dystrophy, Huntington's disease, and spinocerebellar ataxia type 1 [8].
• Microtubule-associated protein tau forms neurofibrillary lesions in Alzheimer's disease and several other neurodegenerative disorders, such as Niemann-Pick disease type C, subacute sclerosing panencephalitis, argyrophilic grain disease, myotonic dystrophy and motor neuron disease with neurofibrillary tangles [9].

High impact information on Myotonic Dystrophy

• Myotonic dystrophy type 1 (DM1) is caused by a CTG trinucleotide expansion in the 3' untranslated region of the DM protein kinase gene [10].
• Our results suggest that SIX5 deficiency contributes to the cataract phenotype in myotonic dystrophy, and that myotonic dystrophy represents a multigenic disorder [1].
• We report the mapping of a second myotonic dystrophy locus, myotonic dystrophy type 2 (DM2) [11].
• We have identified a five-generation family (MN1) with a genetically distinct form of myotonic dystrophy [11].
• A number of diseases have been attributed to TRE, including Huntington disease and myotonic dystrophy (DM), but attempts at genetic therapy have yet to prove successful [12].

Chemical compound and disease context of Myotonic Dystrophy

• Myotonic dystrophy (DM) results from the amplification of an unstable CTG repeat in the 3' untranslated region of a transcript encoding a putative serine/threonine kinase [13].
• Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy [14].
• Myotonic dystrophy patients showed a peak glucose uptake increment of only 2.6 +/- 0.2-fold over basal contrasted with the disease control value of 6.5 +/- 1.0-fold (P is less than 0.02) and the normal control value of 8.8 +/- 1.1-fold (P is less than 0.01) [3].
• Gastric and esophageal emptying in dystrophia myotonica. Effect of metoclopramide [15].
• Deoxycholic acid in myotonic dystrophy [16].

Biological context of Myotonic Dystrophy

• Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of DMAHP [17].
• Here we show that the relatively short triplet-repeat expansions found in myotonic dystrophy and Friedreich's ataxia confer variegation of expression on a linked transgene in mice [18].
• Cbk1p, a protein similar to the human myotonic dystrophy kinase, is essential for normal morphogenesis in Saccharomyces cerevisiae [19].
• The human ryanodine receptor gene: its mapping to 19q13.1, placement in a chromosome 19 linkage group, and exclusion as the gene causing myotonic dystrophy [20].
• Recent genetic linkage studies have mapped the myotonic dystrophy (DM) locus to 19q13 [21].

Anatomical context of Myotonic Dystrophy

• This suggests that colonic motor dysfunction associated with myotonic dystrophy may be caused by a visceral neuropathy that involves the substance P- and enkephalin-immunoreactive fibers of the smooth muscle [22].
• We have analyzed the intracellular localization of transcripts from the myotonin protein kinase (Mt-PK) gene in fibroblasts and muscle biopsies from myotonic dystrophy patients and normal controls [23].
• We have analysed the mitotic behaviour of expanded CTG repeats in somatic tissues and cultured somatic cells from myotonic dystrophy (DM) fetuses using indirect and direct methods [24].
• Myotonic dystrophy: calcium-dependent phosphatidic acid synthesis in erythrocytes [25].
• Novel isoform of myotonin protein kinase: gene product of myotonic dystrophy is localized in the sarcoplasmic reticulum of skeletal muscle [26].

Gene context of Myotonic Dystrophy

• Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9 [27].
• Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder caused by a CTG expansion in the 3' untranslated region of the DMPK gene [28].
• Identification of transcriptional targets for Six5: implication for the pathogenesis of myotonic dystrophy type 1 [29].
• Myotonic dystrophy is associated with a reduced level of RNA from the DMWD allele adjacent to the expanded repeat [30].
• Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins [31].

Analytical, diagnostic and therapeutic context of Myotonic Dystrophy

• MAIN OUTCOME MEASURES--A relationship between myotonic dystrophy disease onset and length of the GCT repeat allele, parental origin of the disease allele, and results of prenatal diagnosis predictions of disease status were measured [32].
• DESIGN--DNA from patients was examined for the length of the myotonic dystrophy GCT repeat region, using both Southern blot analysis and polymerase chain reaction [32].
• In order to characterize the dynamics of CTG repeat instability in somatic and germline tissue from myotonic dystrophy (DM) males we have used small pool polymerase chain reaction (PCR) in a detailed quantitative analysis of repeat length variation [33].
• In this study we have developed an in vitro cell culture system which displays the majority of the defects previously described for congenital myotonic dystrophy (CDM) muscle in vivo [34].
• During an oral glucose tolerance test the 2 h plasma glucose value was significantly higher in patients with myotonic dystrophy compared to controls, and 5 out of the 7 patients demonstrated hyperinsulinemia [35].

References