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.
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Acknowledgements
We wish to thank the members of the families PKMR60 and M105 who voluntarily participated in this study. We thank Bettina Lipkowitz, Melanie Bienek, Sabine Otto and Vanessa Suckow for expert technical assistance. This research has received funding from the European Union’s Seventh Framework Program under grant agreement number 241995 (project GENCODYS). H-HR was funded by the Max-Planck Society, and AR, MYZ and ZI were supported by the Higher Education Commission of Pakistan (HEC).
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Iqbal, Z., Püttmann, L., Musante, L. et al. Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration. Eur J Hum Genet 24, 392–399 (2016). https://doi.org/10.1038/ejhg.2015.148
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DOI: https://doi.org/10.1038/ejhg.2015.148
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