Bi-allelic IARS mutations in a child with intra-uterine growth retardation, neonatal cholestasis, and mild developmental delay

Clin Genet. 2017 Jun;91(6):913-917. doi: 10.1111/cge.12930. Epub 2017 Feb 22.


Recently, bi-allelic mutations in cytosolic isoleucyl-tRNA synthetase (IARS) have been described in three individuals with growth delay, hepatic dysfunction, and neurodevelopmental disabilities. Here we report an additional subject with this condition identified by whole-exome sequencing. Our findings support the association between this disorder and neonatal cholestasis with distinct liver pathology. Furthermore, we provide functional data on two novel missense substitutions and expand the phenotype to include mild developmental delay, skin hyper-elasticity, and hypervitaminosis D.

Keywords: IARS; cholestasis; connective tissue; development; growth; vitamin D.

Publication types

  • Case Reports

MeSH terms

  • Alleles
  • Amino Acid Sequence / genetics
  • Cholestasis / genetics*
  • Cholestasis / pathology
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Exome Sequencing
  • Fetal Growth Retardation / genetics*
  • Fetal Growth Retardation / pathology
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Isoleucine-tRNA Ligase / genetics*
  • Liver / pathology
  • Male
  • Mutation
  • Pedigree


  • Isoleucine-tRNA Ligase