AGK gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Protein: Acylglycerol kinase
  • An enzyme involved in mitochondrial ATP synthesis and the metabolism of cardiolipin and phospholipids
  • Ubiquitously expressed in the mitochondria of a variety of tissues, with highest expression in the heart, kidney, muscle and brain
  • Regulate cell growth
Clinical phenotype
(OMIM phenotype no.)
  • Cataract 38, autosomal recessive (#614691)
  • Sengers Syndrome (#212350)
  • A type of mitochondrial DNA depletion syndrome also known as cardiomyopathic mitochondrial DNA depletion syndrome-10 (MTDPS10)
Inheritance
  • Autosomal recessive
Ocular features
Systemic featuresCataract 38, autosomal recessive
  • Isolated congenital cataract with no systemic features
Sengers Syndrome
  • Hypertrophic cardiomyopathy from birth leading to cardiac failure, which may cause early mortality if severe
  • Skeletal myopathy causing muscular weakness and hypotonia, leading to delayed motor development
  • Exercise intolerance
  • Lactic acidosis associated with exercise
  • Normal mental development
Key investigations
  • B-scan USS to measure axial length to document microphthalmia and detect any posterior segment abnormalities
  • Electrophysiology
  • TORCH screen
  • MRI brain and orbit
  • Echocardiogram and electrocardiogram
  • Systemic assessment with a paediatrician and other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (cataract)
  • Whole exome sequencing
  • Whole genome sequencing
ManagementOcularSystemic
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

Jump to top


Additional information

Most pathogenic variants in AGK cause Sengers syndrome except a splice site mutation (c.424-3 C>G) which has been reported to cause isolated congenital cataract in three siblings from one consanguineous family.[1]

Jump to top


References

  1.  Aldahmesh MA, Khan AO, Mohamed JY, Alghamdi MH, Alkuraya FS. Identification of a truncation mutation of acylglycerol kinase (AGK) gene in a novel autosomal recessive cataract locus. Hum Mutat. 2012;33(6):960‐962
  2.  Calvo SE, Compton AG, Hershman SG, et al. Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing. Sci Transl Med. 2012;4(118):118ra10
  3.  Mayr JA, Haack TB, Graf E, et al. Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome. Am J Hum Genet. 2012;90(2):314‐320

Jump to top

Updated on November 30, 2020
Was this article helpful?