title: Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome.
abstract: Exome sequencing of an individual with congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis, all typical symptoms of Sengers syndrome, discovered two nonsense mutations in the gene encoding mitochondrial acylglycerol kinase (AGK). Mutation screening of AGK in further individuals with congenital cataracts and cardiomyopathy identified numerous loss-of-function mutations in an additional eight families, confirming the causal nature of AGK deficiency in Sengers syndrome. The loss of AGK led to a decrease of the adenine nucleotide translocator in the inner mitochondrial membrane in muscle, consistent with a role of AGK in driving the assembly of the translocator as a result of its effects on phospholipid metabolism in mitochondria.
authors.affiliation: Department of Paediatrics, Paracelsus Medical University Salzburg, Austria.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Mayr
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Haack
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Graf
authors.forename: Franz A
authors.initials: FA
authors.lastname: Zimmermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieland
authors.forename: Birgit
authors.initials: B
authors.lastname: Haberberger
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: Janbernd
authors.initials: J
authors.lastname: Kirschner
authors.forename: Beat
authors.initials: B
authors.lastname: Steinmann
authors.forename: Matthias R
authors.initials: MR
authors.lastname: Baumgartner
authors.forename: Isabella
authors.initials: I
authors.lastname: Moroni
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lamantea
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rodenburg
authors.forename: Jan
authors.initials: J
authors.lastname: Smeitink
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sperl
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
mesh_terms: D000328:Adult; D000483:Alleles; D009202:Cardiomyopathies / Q000201:enzymology* / Q000235:genetics; D002386:Cataract / Q000201:enzymology* / Q000235:genetics; D002648:Child; D018389:Codon, Nonsense; D059472:Exome; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics; D024101:Mitochondrial Proteins / Q000172:deficiency* / Q000235:genetics; D009132:Muscles / Q000378:metabolism; D010641:Phenotype; D010743:Phospholipids / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency* / Q000235:genetics; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D024101:Mitochondrial Proteins; D010743:Phospholipids; D000226:Mitochondrial ADP, ATP Translocases; D017853:Phosphotransferases (Alcohol Group Acceptor); C025944:acylglycerol kinase