Cardiac and skeletal myopathies: can genotype explain phenotype?
The inherited muscle diseases, skeletal muscle nemaline myopathy and cardiac muscle hypertrophic myopathy (HCM) have been recognised for decades. Recently it has become apparent that mutations in almost any protein component of the sarcomere could cause myopathy. Thus changes in many sarcomeric protein genes can produce a common phenotype. Several recent publications indicate the opposite property: mutations in one sarcomeric protein can produce different muscle disease phenotypes. The most dramatic example of this property is actin, mutations in which are associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, nemaline myopathy and actin myopathy.
Marston
S B
SB
Imperial College School of Medicine at National Heart and Lung Institute, London, UK. s.marston@ic.ac.uk
Hodgkinson
J L
JL
D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000199:Actins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D019943:Amino Acid Substitution; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008958:Models, Molecular; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics*; D017696:Myopathies, Nemaline / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D017354:Point Mutation; D011487:Protein Conformation; D012518:Sarcomeres / Q000648:ultrastructure; D013329:Structure-Activity Relationship; D014335:Tropomyosin / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D019210:Troponin I / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D020107:Troponin T / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D000199:Actins; D009124:Muscle Proteins; D014335:Tropomyosin; D019210:Troponin I; D020107:Troponin T