Myopathies resulting from mutations in sarcomeric proteins.
OBJECTIVE
The past decade has seen the discovery of the major role that mutations in the protein components of the sarcomere plays as a cause of human muscle disease. An overview of the more precise molecular definitions of these diseases is timely.


RESULTS
Recent findings include: the beginnings of an understanding of the role of the sarcomere in controlling muscle gene expression; the theoretical analysis of the increasing number of mutations identified in the skeletal muscle actin gene; the identification of mutations in myosin causing hereditary inclusion body myopathy and hyaline body myopathy and the identification of mutations in myotilin in myofibrillar myopathy.


CONCLUSIONS
An increasing spectrum of human muscle diseases is being shown to be caused by mutations in proteins of all the major components of the sarcomere. Molecular analysis is providing a more accurate delineation of these diseases, but for the giant nebulin and titin genes, molecular diagnosis remains difficult. Treatment options for these disorders will only come through a deeper understanding of the sarcomere and of the pathogenesis of its disorders.
Bönnemann
Carsten G
CG
Division of Neurology and Pennsylvania Muscle Institute, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. bonnemann@email.chop.edu
Laing
Nigel G
NG
D000199:Actins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D012518:Sarcomeres / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure
D000199:Actins; D009124:Muscle Proteins