Title

Biallelic Loss-of-Function Variants in AIMP1 Cause a Rare Neurodegenerative Disease.

Document Type

Article

Publication Date

2-1-2019

Abstract

AIMP1/p43, is a noncatalytic component of the mammalian multi-tRNA synthetase complex that catalyzes the ligation of amino acids to their cognate tRNAs. AIMP1 is largely expressed in the central nervous system, where it is part of the regulatory machine of the neurofilament assembly, playing a crucial role in neuronal development and function. To date, nonsense mutations in AIMP1 have been associated with a primary neurodegenerative disorder consisting of cerebral atrophy, hypomyelination, microcephaly and epilepsy, whereas missense mutations have recently been linked to intellectual disability without neurodegeneration. Here, we report the first French-Canadian patient with a novel frameshift AIMP1 homozygous mutation (c.191_192delAA, p.Gln64Argfs*25), resulting in a severe neurodegenerative phenotype. We review and discuss the phenotypic spectrum associated with AIMP1 pathogenic variants.

Journal Title

Journal of child neurology

Volume

34

Issue

2

First Page

74

Last Page

80

MeSH Keywords

Atrophy; Brain; Child, Preschool; Cytokines; Demyelinating Diseases; Epilepsy; Female; Frameshift Mutation; Humans; Microcephaly; Neoplasm Proteins; Neurodegenerative Diseases; RNA-Binding Proteins

Keywords

intellectual disability; leukodystrophy; neurodevelopment; seizures; spasticity

Comments

Grant support

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