title: Fatal hypertrophic cardiomyopathy and nemaline myopathy associated with ACTA1 K336E mutation.
abstract: 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.
authors.affiliation: Unit of Molecular Medicine and Pathology, Dept. of Laboratory Medicine, Bambino Gesu' Children's Research Hospital, Rome, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: D'Amico
authors.forename: Claudio
authors.initials: C
authors.lastname: Graziano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pacileo
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrini
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Nowak
authors.forename: Renata
authors.initials: R
authors.lastname: Boldrini
authors.forename: Adam
authors.initials: A
authors.lastname: Jacques
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Feng
authors.forename: Berardino
authors.initials: B
authors.lastname: Porfirio
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sewry
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Limongelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Nigel
authors.initials: N
authors.lastname: Laing
authors.forename: Steven B
authors.initials: SB
authors.lastname: Marston
mesh_terms: 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
chemical_list: D000199:Actins; D000185:Actinin; D018698:Glutamic Acid; D008239:Lysine