Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy.

Abstract

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.

• Authors: Robert Kopajtich, Kei Murayama, Andreas R Janecke, Tobias B Haack, Maximilian Breuer, A S Knisely, Inga Harting, Toya Ohashi, Yasushi Okazaki, Daisaku Watanabe, Yoshimi Tokuzawa, Urania Kotzaeridou, Stefan Kölker, Sven Sauer, Matthias Carl, Simon Straub, Andreas Entenmann, Elke Gizewski, René G Feichtinger, Johannes A Mayr, Karoline Lackner, Tim M Strom, Thomas Meitinger, Thomas Müller, Akira Ohtake, Georg F Hoffmann, Holger Prokisch, Christian Staufner
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 99 Issue 2 Pg. 414-22 (Aug 04 2016) ISSN: 1537-6605 [Electronic] United States
• PMID: 27426735 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Chemical References

• Isoleucine-tRNA Ligase
• Zinc

Topics

• 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, genetics)
• Liver Diseases (congenital, genetics)
• Liver Failure (genetics)
• Male
• Muscle Hypotonia (congenital, genetics)
• Mutation
• Syndrome
• Zebrafish (genetics)
• Zinc (administration & dosage, deficiency, therapeutic use)