title: Severe nemaline myopathy caused by mutations of the stop codon of the skeletal muscle alpha actin gene (ACTA1).
abstract: 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.
authors.affiliation: 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.
authors.forename: William
authors.initials: W
authors.lastname: Wallefeld
authors.forename: Sabine
authors.initials: S
authors.lastname: Krause
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Nowak
authors.forename: Danielle
authors.initials: D
authors.lastname: Dye
authors.forename: Rita
authors.initials: R
authors.lastname: Horváth
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Molnár
authors.forename: Miklós
authors.initials: M
authors.lastname: Szabó
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Cristina
authors.initials: C
authors.lastname: Reina
authors.forename: Jose
authors.initials: J
authors.lastname: De Carlos
authors.forename: Jordi
authors.initials: J
authors.lastname: Rosell
authors.forename: Ana
authors.initials: A
authors.lastname: Cabello
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Laing
mesh_terms: 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
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; D018388:Codon, Terminator; D011993:Recombinant Fusion Proteins