Pathogenic variants in AIMP1 cause pontocerebellar hypoplasia

Neurogenetics. 2019 May;20(2):103-108. doi: 10.1007/s10048-019-00572-7. Epub 2019 Mar 28.

Abstract

Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the multi-tRNA synthetase complex which catalyzes the ligation of amino acids to the correct tRNAs. Pathogenic variants in several aminoacyl-tRNA synthetases genes have been linked to various neurological disorders, including leukodystrophies and pontocerebellar hypoplasias (PCH). To date, loss-of-function variants in AIMP1 have been associated with hypomyelinating leukodystrophy-3 (MIM 260600). Here, we report a novel frameshift AIMP1 homozygous variant (c.160delA,p.Lys54Asnfs) in a child with pontocerebellar hypoplasia and simplified gyral pattern, a phenotype not been previously described with AIMP1 variants, thus expanding the phenotypic spectrum. AIMP1 should be included in diagnostic PCH gene panels.

Keywords: AIMP1/p43; Aminoacyl-tRNA synthetases; Hypomyelinating leukodystrophy; Pontocerebellar hypoplasia.

Publication types

  • Case Reports

MeSH terms

  • Cerebellar Diseases / genetics*
  • Cytokines / genetics*
  • Cytosol / metabolism
  • Fatal Outcome
  • Frameshift Mutation
  • Gene Deletion
  • Genetic Predisposition to Disease*
  • Heterozygote
  • Homozygote
  • Humans
  • Infant
  • Male
  • Mitochondria / metabolism
  • Myelin Sheath / metabolism
  • Neoplasm Proteins / genetics*
  • Pelizaeus-Merzbacher Disease / genetics*
  • Phenotype
  • Protein Biosynthesis
  • Protein Denaturation
  • Protein Folding
  • Protein Isoforms
  • RNA-Binding Proteins / genetics*

Substances

  • Cytokines
  • Neoplasm Proteins
  • Protein Isoforms
  • RNA-Binding Proteins
  • small inducible cytokine subfamily E, member 1

Supplementary concepts

  • Pontocerebellar Hypoplasia