Homozygosity for a nonsense variant in AIMP2 is associated with a progressive neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis

Anju Shukla, Aneek Das Bhowmik, Malavika Hebbar, Kadavigere V. Rajagopal, Katta M. Girisha, Neerja Gupta, Ashwin Dalal

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)19-25
Number of pages7
JournalJournal of Human Genetics
Volume63
Issue number1
DOIs
Publication statusPublished - 01-01-2018

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Microcephaly
Quadriplegia
Muscle Spasticity
Seizures
Cisterna Magna
Exome
Mutation
Chromosomes, Human, Pair 7
Corpus Callosum
Cerebrum
Basal Ganglia
Intellectual Disability
Cerebellum
Atrophy
Spinal Cord
Magnetic Resonance Imaging
Phenotype
Genes
Neurodevelopmental Disorders
Pelizaeus-Merzbacher-like disease, autosomal recessive, 2

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

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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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Homozygosity for a nonsense variant in AIMP2 is associated with a progressive neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis. / Shukla, Anju; Das Bhowmik, Aneek; Hebbar, Malavika; Rajagopal, Kadavigere V.; Girisha, Katta M.; Gupta, Neerja; Dalal, Ashwin.

In: Journal of Human Genetics, Vol. 63, No. 1, 01.01.2018, p. 19-25.

Research output: Contribution to journalArticle

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AU - Shukla, Anju

AU - Das Bhowmik, Aneek

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AU - Gupta, Neerja

AU - Dalal, Ashwin

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