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Eur J Hum Genet. 2016 Mar;24(3):392-9. doi: 10.1038/ejhg.2015.148. Epub 2015 Jul 15.

Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration.

Author information

1
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
2
Max-Planck Institute for Molecular Genetics, Berlin, Germany.
3
National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
4
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
5
Kariminejad-Najmabadi Pathology & Genetics Center Tehran, Tehran, Iran.
6
Allama Iqbal Medical College, Lahore, Pakistan.
7
Department of Cognitive Neurosciences, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.

Abstract

AIMP1/p43 is a multifunctional non-catalytic component of the multisynthetase complex. The complex consists of nine catalytic and three non-catalytic proteins, which catalyze the ligation of amino acids to their cognate tRNA isoacceptors for use in protein translation. To date, two allelic variants in the AIMP1 gene have been reported as the underlying cause of autosomal recessive primary neurodegenerative disorder. Here, we present two consanguineous families from Pakistan and Iran, presenting with moderate to severe intellectual disability, global developmental delay, and speech impairment without neurodegeneration. By the combination of homozygosity mapping and next generation sequencing, we identified two homozygous missense variants, p.(Gly299Arg) and p.(Val176Gly), in the gene AIMP1 that co-segregated with the phenotype in the respective families. Molecular modeling of the variants revealed deleterious effects on the protein structure that are predicted to result in reduced AIMP1 function. Our findings indicate that the clinical spectrum for AIMP1 defects is broader than witnessed so far.

PMID:
26173967
PMCID:
PMC4755381
[Available on 2017-03-01]
DOI:
10.1038/ejhg.2015.148
[Indexed for MEDLINE]
Free PMC Article

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