Linked Life Data

10508519

Source:http://linkedlifedata.com/resource/pubmed/id/10508519

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-10-19
pubmed:databankReference
pubmed:abstractText
Muscle contraction results from the force generated between the thin filament protein actin and the thick filament protein myosin, which causes the thick and thin muscle filaments to slide past each other. There are skeletal muscle, cardiac muscle, smooth muscle and non-muscle isoforms of both actin and myosin. Inherited diseases in humans have been associated with defects in cardiac actin (dilated cardiomyopathy and hypertrophic cardiomyopathy), cardiac myosin (hypertrophic cardiomyopathy) and non-muscle myosin (deafness). Here we report that mutations in the human skeletal muscle alpha-actin gene (ACTA1) are associated with two different muscle diseases, 'congenital myopathy with excess of thin myofilaments' (actin myopathy) and nemaline myopathy. Both diseases are characterized by structural abnormalities of the muscle fibres and variable degrees of muscle weakness. We have identified 15 different missense mutations resulting in 14 different amino acid changes. The missense mutations in ACTA1 are distributed throughout all six coding exons, and some involve known functional domains of actin. Approximately half of the patients died within their first year, but two female patients have survived into their thirties and have children. We identified dominant mutations in all but 1 of 14 families, with the missense mutations being single and heterozygous. The only family showing dominant inheritance comprised a 33-year-old affected mother and her two affected and two unaffected children. In another family, the clinically unaffected father is a somatic mosaic for the mutation seen in both of his affected children. We identified recessive mutations in one family in which the two affected siblings had heterozygous mutations in two different exons, one paternally and the other maternally inherited. We also identified de novo mutations in seven sporadic probands for which it was possible to analyse parental DNA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
208-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10508519-Actins, pubmed-meshheading:10508519-Adolescent, pubmed-meshheading:10508519-Adult, pubmed-meshheading:10508519-Amino Acid Sequence, pubmed-meshheading:10508519-Amino Acid Substitution, pubmed-meshheading:10508519-Base Sequence, pubmed-meshheading:10508519-Child, pubmed-meshheading:10508519-Child, Preschool, pubmed-meshheading:10508519-DNA, pubmed-meshheading:10508519-DNA Mutational Analysis, pubmed-meshheading:10508519-Family Health, pubmed-meshheading:10508519-Female, pubmed-meshheading:10508519-Humans, pubmed-meshheading:10508519-Infant, pubmed-meshheading:10508519-Male, pubmed-meshheading:10508519-Molecular Sequence Data, pubmed-meshheading:10508519-Muscle, Skeletal, pubmed-meshheading:10508519-Muscular Diseases, pubmed-meshheading:10508519-Mutation, pubmed-meshheading:10508519-Myopathies, Nemaline, pubmed-meshheading:10508519-Point Mutation, pubmed-meshheading:10508519-Polymorphism, Genetic, pubmed-meshheading:10508519-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:10508519-Sequence Analysis, DNA, pubmed-meshheading:10508519-Sequence Homology, Amino Acid
pubmed:year
1999
pubmed:articleTitle
Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy.
pubmed:affiliation
Centre for Neuromuscular Disorders, University of Western Australia, Nedlands, Western Australia 6009, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't