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

Iqbal, Z.; Püttmann, L.; Musante, L.; Razzaq, A.; Zahoor, M. Y.; Hu, H.; Wienker, T. F.; Garshasbi, M.; Fattahi, Z.; Gilissen, C.; Vissers, L. E.; de Brouwer, A. P.; Veltman, J. A.; Pfundt, R.; Najmabadi, H.; Ropers, H. H.; Riazuddin, S.; Kahrizi, K.; van Bokhoven, H.

doi:10.1038/ejhg.2015.148

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

MPS-Authors

Püttmann, L.
Emeritus Group of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Musante, L.
Emeritus Group of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

Hu, H.
Emeritus Group of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Wienker, T. F.
Clinical Genetics (Thomas F. Wienker), Emeritus Group of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

Garshasbi, M.
Emeritus Group of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Ropers, H. H.
Emeritus Group of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

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http://www.ncbi.nlm.nih.gov/pubmed/26173967
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Citation

Iqbal, Z., Püttmann, L., Musante, L., Razzaq, A., Zahoor, M. Y., Hu, H., et al. (2016). Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration. European journal of human genetics, 24(3), 392-399. doi:10.1038/ejhg.2015.148.

Cite as: https://hdl.handle.net/21.11116/0000-0000-C17A-D

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.