ZFIN ID: ZDB-PUB-170125-12
Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy
Kopajtich, R., Murayama, K., Janecke, A.R., Haack, T.B., Breuer, M., Knisely, A.S., Harting, I., Ohashi, T., Okazaki, Y., Watanabe, D., Tokuzawa, Y., Kotzaeridou, U., Kölker, S., Sauer, S., Carl, M., Straub, S., Entenmann, A., Gizewski, E., Feichtinger, R.G., Mayr, J.A., Lackner, K., Strom, T.M., Meitinger, T., Müller, T., Ohtake, A., Hoffmann, G.F., Prokisch, H., Staufner, C.
Date: 2016
Source: American journal of human genetics   99(2): 414-22 (Journal)
Registered Authors: Breuer, Maximilian, Carl, Matthias
Keywords: none
MeSH Terms:
  • Adolescent
  • Alleles*
  • Animals
  • Child
  • Child, Preschool
  • Dietary Supplements
  • Fatty Liver/genetics
  • Female
  • Fetal Growth Retardation/genetics*
  • Fibrosis/genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Intellectual Disability/genetics*
  • Isoleucine-tRNA Ligase/deficiency
  • Isoleucine-tRNA Ligase/genetics*
  • Liver Diseases/congenital*
  • Liver Diseases/genetics*
  • Liver Failure/genetics
  • Male
  • Muscle Hypotonia/congenital*
  • Muscle Hypotonia/genetics*
  • Mutation*
  • Syndrome
  • Zebrafish/genetics
  • Zinc/administration & dosage
  • Zinc/deficiency
  • Zinc/therapeutic use
PubMed: 27426735 Full text @ Am. J. Hum. Genet.
tRNA synthetase deficiencies are a growing group of genetic diseases associated with tissue-specific, mostly neurological, phenotypes. In cattle, cytosolic isoleucyl-tRNA synthetase (IARS) missense mutations cause hereditary weak calf syndrome. Exome sequencing in three unrelated individuals with severe prenatal-onset growth retardation, intellectual disability, and muscular hypotonia revealed biallelic mutations in IARS. Studies in yeast confirmed the pathogenicity of identified mutations. Two of the individuals had infantile hepatopathy with fibrosis and steatosis, leading in one to liver failure in the course of infections. Zinc deficiency was present in all affected individuals and supplementation with zinc showed a beneficial effect on growth in one.