Severe nemaline myopathy caused by mutations of the stop codon of the skeletal muscle alpha actin gene (ACTA1).
Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes. Here we report for the first time three patients with severe nemaline myopathy and mutations of the ACTA1 stop codon: TAG>TAT (tyrosine), TAG>CAG (glutamine) and TAG>TGG (tryptophan). All three mutations will cause inclusion of an additional 47 amino acids, translated from the 3' UTR of the gene, into the mature actin protein. Western blotting of one patient's muscle demonstrated the presence of the larger protein, while expression of one of the other mutant proteins fused to EGFP in C2C12 cells demonstrated the formation of rod bodies.
Wallefeld
William
W
Molecular Neurogenetics Laboratory, Centre for Medical Research, University of Western Australia, Western Australian Institute for Medical Research, B Block, Queen Elizabeth II Medical Centre, Nedlands, WA 6009, Australia.
Krause
Sabine
S
Nowak
Kristen J
KJ
Dye
Danielle
D
Horváth
Rita
R
Molnár
Zoltán
Z
Szabó
Miklós
M
Hashimoto
Kazuhiro
K
Reina
Cristina
C
De Carlos
Jose
J
Rosell
Jordi
J
Cabello
Ana
A
Navarro
Carmen
C
Nishino
Ichizo
I
Lochmüller
Hanns
H
Laing
Nigel G
NG
D020413:3' Untranslated Regions / Q000235:genetics; D000199:Actins / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002675:Child, Preschool; D018388:Codon, Terminator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D017696:Myopathies, Nemaline / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D000199:Actins; D018388:Codon, Terminator; D011993:Recombinant Fusion Proteins