Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome

Am J Hum Genet. 2012 Feb 10;90(2):314-20. doi: 10.1016/j.ajhg.2011.12.005. Epub 2012 Jan 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Cardiomyopathies / enzymology*
  • Cardiomyopathies / genetics
  • Cataract / enzymology*
  • Cataract / genetics
  • Child
  • Codon, Nonsense*
  • Exome
  • Female
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mitochondria / enzymology*
  • Mitochondria / genetics
  • Mitochondrial ADP, ATP Translocases / genetics
  • Mitochondrial Proteins / deficiency*
  • Mitochondrial Proteins / genetics
  • Muscles / metabolism
  • Phenotype
  • Phospholipids / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / deficiency*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Young Adult

Substances

  • Codon, Nonsense
  • Mitochondrial Proteins
  • Phospholipids
  • Mitochondrial ADP, ATP Translocases
  • Phosphotransferases (Alcohol Group Acceptor)
  • acylglycerol kinase

Supplementary concepts

  • Cataract and cardiomyopathy