title: Bi-allelic IARS mutations in a child with intra-uterine growth retardation, neonatal cholestasis, and mild developmental delay.
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.
authors.affiliation: Department of Pediatric Genetics, Schneider Children Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Orenstein
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: K
authors.initials: K
authors.lastname: Weiss
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Oprescu
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Shapira
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Department of Pathology, Meir Hospital, Kfar Saba, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Kidron
authors.affiliation: Department of Pediatric Genetics, Schneider Children Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Raphael Recanati Genetics Institute, Rabin Medical Center, Petah Tikva, Israel.|Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikvay, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Vanagaite-Basel
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Antonellis
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Muenke
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D002779:Cholestasis / Q000235:genetics* / Q000473:pathology; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007533:Isoleucine-tRNA Ligase / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D000073359:Exome Sequencing
chemical_list: D007533:Isoleucine-tRNA Ligase
keywords: IARS; cholestasis; connective tissue; development; growth; vitamin D