Fatal hypertrophic cardiomyopathy and nemaline myopathy associated with ACTA1 K336E mutation.
We report on a 2-year-old male child with both nemaline myopathy and hypertrophic cardiomyopathy (HCM). Sequencing of the ACTA1 gene showed a "de novo" missense heterozygous mutation a>g in exon 7 (Lys336Glu). Two-dimensional electrophoresis showed 28% mutant actin present in his muscle biopsy. Actin was isolated from the muscle biopsy and examined by in vitro motility assay. The sliding speed was 13+/-3% less than normal and the affinity of actin for the Z-line protein alpha-actinin was reduced 10 fold. This is the first report on a hypertrophic cardiomyopathy associated with nemaline myopathy and an ACTA1 mutation.
D'Amico
Adele
A
Unit of Molecular Medicine and Pathology, Dept. of Laboratory Medicine, Bambino Gesu' Children's Research Hospital, Rome, Italy.
Graziano
Claudio
C
Pacileo
Giuseppe
G
Petrini
Stefania
S
Nowak
Kristen J
KJ
Boldrini
Renata
R
Jacques
Adam
A
Feng
Juan-Juan
JJ
Porfirio
Berardino
B
Sewry
Caroline A
CA
Santorelli
Filippo M
FM
Limongelli
Giuseppe
G
Bertini
Enrico
E
Laing
Nigel
N
Marston
Steven B
SB
D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D008297:Male; D009119:Muscle Contraction / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D017696:Myopathies, Nemaline / Q000150:complications / Q000235:genetics* / Q000503:physiopathology
D000199:Actins; D000185:Actinin; D018698:Glutamic Acid; D008239:Lysine