Linked Life Data

14724127

Source:http://linkedlifedata.com/resource/pubmed/id/14724127

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 4
pubmed:dateCreated
2004-3-26
pubmed:abstractText
Desmin myopathy is a recently identified disease associated with mutations in desmin or alphaB-crystallin. Typically, the illness presents with lower limb muscle weakness slowly spreading to involve truncal, neck-flexor, facial, bulbar and respiratory muscles. Skeletal myopathy is often combined with cardiomyopathy manifested by conduction blocks and arrhythmias resulting in premature sudden death. Sections of the affected skeletal and cardiac muscles show abnormal fibre areas containing amorphous eosinophilic deposits seen as granular or granulofilamentous material on electron microscopic examination. Immuno-staining for desmin is positive in each region containing abnormal structures. The inheritance pattern in familial desmin myopathy is autosomal dominant or autosomal recessive, but many cases have no family history. At least some, and probably most, non-familial desmin myopathy cases are associated with de novo desmin mutations. Age of disease onset and rate of progression may vary depending on the type of inheritance and location of the causative mutation. Multiple mutations have been identified in the desmin gene: point substitutions, insertion, small in-frame deletions and a larger exon-skipping deletion. The majority of these mutations are located in conserved alpha-helical segments of desmin. Many of the missense mutations result in changing the original amino acid into proline, which is known as a helix breaker. Studies of transfected cell cultures indicate that mutant desmin is assembly-incompetent and able to disrupt a pre-existing filamentous network in dominant-negative fashion. Disease-associated desmin mutations in humans or transgenic mice cause accumulation of chimeric intracellular aggregates containing desmin and other cytoskeletal proteins. alphaB-crystallin serves in the muscle as a chaperone preventing desmin aggregation under various forms of stress. If mutated, alphaB-crystallin may cause a myopathy similar to those resulting from desmin mutations. Routine genetic testing of patients for mutations in desmin and alphaB- crystallin genes is now available and necessary for establishing an accurate diagnosis and providing appropriate genetic counselling. Better understanding of disease pathogenesis would stimulate research focused on developing specific treatments for these conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-8950
pubmed:author
pubmed:issnType
Print
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
723-34
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Desmin myopathy.
pubmed:affiliation
National Institutes of Health, Bethesda, MD 20892-1361, USA. goldfarbl@ninds.nih.gov
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't