title: Exome sequencing identifies MRPL3 mutation in mitochondrial cardiomyopathy.
abstract: By combining exome sequencing in conjunction with genetic mapping, we have identified the first mutation in large mitochondrial ribosomal protein MRPL3 in a family of four sibs with hypertrophic cardiomyopathy, psychomotor retardation, and multiple respiratory chain deficiency. Affected sibs were compound heterozygotes for a missense MRPL3 mutation (P317R) and a large-scale deletion, inherited from the mother and the father, respectively. These mutations were shown to alter ribosome assembly and cause a mitochondrial translation deficiency in cultured skin fibroblasts resulting in an abnormal assembly of several complexes of the respiratory chain. This observation gives support to the view that exome sequencing combined with genetic mapping is a powerful approach for the identification of new genes of mitochondrial disorders.
authors.affiliation: Department of Genetics, INSERM U781, Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France.
authors.forename: Louise
authors.initials: L
authors.lastname: Galmiche
authors.forename: Valérie
authors.initials: V
authors.lastname: Serre
authors.forename: Marine
authors.initials: M
authors.lastname: Beinat
authors.forename: Zahra
authors.initials: Z
authors.lastname: Assouline
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Lebre
authors.forename: Dominique
authors.initials: D
authors.lastname: Chretien
authors.forename: Patrick
authors.initials: P
authors.lastname: Nietschke
authors.forename: Vladimir
authors.initials: V
authors.lastname: Benes
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Daniel
authors.initials: D
authors.lastname: Sidi
authors.forename: Francis
authors.initials: F
authors.lastname: Brunelle
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Agnès
authors.initials: A
authors.lastname: Rötig
mesh_terms: D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000737:chemistry; D059472:Exome; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; C572431:MRPL3 protein, human; D024101:Mitochondrial Proteins; D012269:Ribosomal Proteins