Bi-allelic IARS mutations in a child with intra-uterine growth retardation, neonatal cholestasis, and mild developmental delay
Related Experiment Video
Updated: Mar 11, 2026
Isolation of Neonatal Extrahepatic Cholangiocytes
Published on: June 5, 2014
N Orenstein1,2, K Weiss3, S N Oprescu4
1Department of Pediatric Genetics, Schneider Children Medical Center of Israel, Petah Tikva, Israel.
Insights
Bi-allelic mutations in cytosolic isoleucyl-tRNA synthetase (IARS) cause growth delay and liver issues. This study identifies a new patient, expanding the known symptoms of this rare genetic disorder.
Area of Science:
- Genetics
- Molecular Biology
- Pediatrics
Background:
- Bi-allelic mutations in cytosolic isoleucyl-tRNA synthetase (IARS) have been linked to a rare genetic disorder.
- Previous reports identified three individuals with growth delay, hepatic dysfunction, and neurodevelopmental disabilities.
Observation:
- This report details an additional subject diagnosed with this IARS-related condition via whole-exome sequencing.
- The study highlights a distinct liver pathology associated with neonatal cholestasis in affected individuals.
Findings:
- Two novel missense substitutions in IARS were identified and functionally characterized.
- The clinical phenotype associated with IARS mutations is expanded to include mild developmental delay, skin hyper-elasticity, and hypervitaminosis D.
Implications:
- These findings reinforce the association between IARS mutations and a specific spectrum of developmental and metabolic disorders.
- Further research into IARS function and related pathologies may reveal new therapeutic targets.
Abstract:
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.
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