Duchenne Muscular Dystrophy (DMD)
| Dred_ID | RD00053 |
| OMIM ID | 300377 |
| Disease name | Duchenne Muscular Dystrophy |
| Alternative names | DMD |
| Category | Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Muscle diseases |
| Phenotype | OMIM: Dystrophinopathies are allelic X-linked myopathies caused by large deletions/duplications or small lesions along theDMDgene. An unexpected dynamic trinucleotide (GAA) expansion, ranging from ~59 to 82 pure GAA repeats, within theDMDintron 62, was revealed to segregate through three family generations. From the pedigree, two female patients were referred for DMD investigation due to chronic myopathy and a muscle biopsy compatible with dystrophinopathy. |
| Miscellaneouse | OMIM: usual onset before age 6 years and death by age 20 incidence of 1 in 3,500 boys about 20% of female mutation carriers may show mild muscle weakness about 8% of female mutation carriers develop dilated cardiomyopathy |
| Prevalence | Prevalence: 1-9/100000 (Europe),1-9/100000 (United Kingdom),1-5/10000 (Europe),1-9/100000 (Ireland),1-9/100000 (Italy),1-9/100000 (Worldwide),1-9/100000 (Egypt),1-9/100000 (Japan),1-9/1000000 (South Africa),1-9/100000 (Denmark),1-9/100000 (Puerto rico); [source: MalaCards] |
| Inheritance | X-linked recessive |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | DMD |
| Alias symbols | BMD; CMD3B; MRX85; DXS142; DXS164 |
| Gene name | dystrophin |
| Gene map locus | Xp21.2-p21.1; chrX:31,097,677-33,339,609(-) |
| Ensembl Gene ID | ENSG00000198947 |
| 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 | The dystrophin gene is the largest gene found in nature, measuring 2.4 Mb. The gene was identified through a positional cloning approach, targeted at the isolation of the gene responsible for Duchenne (DMD) and Becker (BMD) Muscular Dystrophies. DMD is a recessive, fatal, X-linked disorder occurring at a frequency of about 1 in 3,500 new-born males. BMD is a milder allelic form. In general, DMD patients carry mutations which cause premature translation termination (nonsense or frame shift mutations), while in BMD patients dystrophin is reduced either in molecular weight (derived from in-frame deletions) or in expression level. The dystrophin gene is highly complex, containing at least eight independent, tissue-specific promoters and two polyA-addition sites. Furthermore, dystrophin RNA is differentially spliced, producing a range of different transcripts, encoding a large set of protein isoforms. Dystrophin (as encoded by the Dp427 transcripts) is a large, rod-like cytoskeletal protein which is found at the inner surface of muscle fibers. Dystrophin is part of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton (F-actin) and the extra-cellular matrix. [provided by RefSeq, Dec 2016] |
| Repeat unit | GAA |
| Normal repeat copies | 11-33 |
| Pathogenic repeat copies | ≥59 |
| Gene | DMD |
| Repeat location | intron |
| Chromosome locus | chrX:31284555-31284605 (-) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | GAA tracts in both FXN and DMD genes are closely linked to a 5′ polyA sequence of 16 and 8 residuals long, respectively. In the case of the GAA expansion disclosed in this study a constant motif {GAGAAGAAGA (GAA)19} was introduced in combination with the loss of three adenine bases. A stabilizing nature for the GAGAAGAAGA sequence could be postulated to interrupt pure GAA tracts thus obstructing the formation of anomalous structures and sticky DNA. [PMID: 27417533] |
| Pathway annotation | Reactome, KEGG |
| PMID | 27417533 |
| Authors | Kekou K, Sofocleous C, Papadimas G, Petichakis D, et al. |
| Title | A dynamic trinucleotide repeat (TNR) expansion in the DMD gene |
| Journal | Mol Cell Probes. 2016 Aug. 30(4):254-60 |
| Year | 2016 |