title: A Novel Alpha Cardiac Actin (ACTC1) Mutation Mapping to a Domain in Close Contact with Myosin Heavy Chain Leads to a Variety of Congenital Heart Defects, Arrhythmia and Possibly Midline Defects.
abstract: BACKGROUND
  A Lebanese Maronite family presented with 13 relatives affected by various congenital heart defects (mainly atrial septal defects), conduction tissue anomalies and midline defects. No mutations were found in GATA4 and NKX2-5.
  
  
  RESULTS
  A set of 399 poly(AC) markers was used to perform a linkage analysis which peaked at a 2.98 lod score on the long arm of chromosome 15. The haplotype analysis delineated a 7.7 meganucleotides genomic interval which included the alpha-cardiac actin gene (ACTC1) among 36 other protein coding genes. A heterozygous missense mutation was found (c.251T>C, p.(Met84Thr)) in the ACTC1 gene which changed a methionine residue conserved up to yeast. This mutation was absent from 1000 genomes and exome variant server database but segregated perfectly in this family with the affection status. This mutation and 2 other ACTC1 mutations (p.(Glu101Lys) and p.(Met125Val)) which result also in congenital heart defects are located in a region in close apposition to a myosin heavy chain head region by contrast to 3 other alpha-cardiac actin mutations (p.(Ala297Ser),p.(Asp313His) and p.(Arg314His)) which result in diverse cardiomyopathies and are located in a totally different interaction surface.
  
  
  CONCLUSIONS
  Alpha-cardiac actin mutations lead to congenital heart defects, cardiomyopathies and eventually midline defects. The consequence of an ACTC1 mutation may in part be dependent on the interaction surface between actin and myosin.
authors.affiliation: EA 4173, Université Lyon 1 and Hôpital Nord-Ouest, Lyon, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Augière
authors.affiliation: IBCP, UMR 5305 CNRS and Université Lyon 1, Lyon, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Mégy
authors.affiliation: Laboratoire Cardiogénétique Malformation, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Bron, France.
authors.forename: Rajae
authors.initials: R
authors.lastname: El Malti
authors.affiliation: Centre National de Génotypage, Evry, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Boland
authors.affiliation: EA 4173, Université Lyon 1 and Hôpital Nord-Ouest, Lyon, France.
authors.forename: Loubna
authors.initials: L
authors.lastname: El Zein
authors.affiliation: IBCP, UMR 5305 CNRS and Université Lyon 1, Lyon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.affiliation: Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon; Institut Jérôme Lejeune, Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
authors.affiliation: IBCP, UMR 5305 CNRS and Université Lyon 1, Lyon, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Deleuze
authors.affiliation: EA 4173, Université Lyon 1 and Hôpital Nord-Ouest, Lyon, France; Laboratoire Cardiogénétique Malformation, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Bron, France; Service de Cardiologie Pédiatrique, Hôpital Louis Pradel, Hospices Civils de Lyon, Bron, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Bouvagnet
mesh_terms: D000199:Actins / Q000235:genetics*; D001145:Arrhythmias, Cardiac / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007861:Lebanon; D008297:Male; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D017434:Protein Structure, Tertiary
chemical_list: C526913:ACTC1 protein, human; D000199:Actins; D005819:Genetic Markers; D018995:Myosin Heavy Chains