Abstract
We ascertained two unrelated consanguineous families with two affected children each having microcephaly, refractory seizures, intellectual disability, and spastic quadriparesis. Magnetic resonance imaging showed atrophy of cerebrum, cerebellum and spinal cord, prominent cisterna magna, symmetric T2 hypo-intensities in the bilateral basal ganglia and thinning of corpus callosum. Whole-exome sequencing of three affected individuals revealed c.105C>A [p.(Tyr35Ter)] variant in AIMP2. The variant lies in a common homozygous region of 940 kb on chromosome 7 and is likely to have been inherited from a common ancestor. The phenotype noted in our subjects’ shares marked similarity with that of hypomyelinating leukodystrophy-3 caused by mutations in closely related gene AIMP1. We hereby report the first human disease associated with deleterious mutations in AIMP2.
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Acknowledgements
We thank the families who cooperated with the evaluation of the subjects and consented for participation in this study. We are also thankful to Dr. Vineeth VS & Dr. Usha R Dutta from Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad for assisting in RT-qPCR experiment. Our sincere thanks to Ms. Priyanka Bhakt and Dr. Rupinder Kaur from the Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad for assisting in statistical analysis of RT-qPCR using GraphPad Prism software.
Funding
This work was supported by the Department of Health Research, which funded the project titled “Clinical and molecular characterization of leukodystrophies in Indian children” (V.25011/379/2015-GIA/HR) and Science and Engineering Research Board (SERB), Government of India (SERB file no. YSS/2015/001681) and Department of Biotechnology, Government of India, Grant Number: BT/PR3193/MED/12/521/2011.
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Shukla, A., Das Bhowmik, A., Hebbar, M. et al. Homozygosity for a nonsense variant in AIMP2 is associated with a progressive neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis. J Hum Genet 63, 19–25 (2018). https://doi.org/10.1038/s10038-017-0363-1
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DOI: https://doi.org/10.1038/s10038-017-0363-1
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