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Severe growth deficiency, microcephaly, intellectual disability, and characteristic facial features are due to a homozygous QARS mutation
- Source :
- Neurogenetics. 18(3)
- Publication Year :
- 2017
-
Abstract
- Glutaminyl tRNA synthase is highly expressed in the developing fetal human brain. Mutations in the glutaminyl-tRNA synthetase (QARS) gene have been reported in patients with progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. We have previously reported a new recessive syndrome of severe linear growth retardation, poor weight gain, microcephaly, characteristic facial features, cutaneous syndactyly of the toes, high myopia, and intellectual disability in two sisters of Ashkenazi-Jewish origin (Eur J Med Genet 2014;57(6):288-92). Homozygosity mapping and whole exome sequencing revealed a homozygous missense (V476I) mutation in the QARS gene, located in the catalytic domain. The patient's fibroblasts demonstrated markedly reduced QARS amino acylation activity in vitro. Furthermore, the same homozygous mutation was found in an unrelated girl of Ashkenazi origin with the same phenotype. The clinical presentation of our patients differs from the original QARS-associated syndrome in the severe postnatal growth failure, absence of epilepsy, and minor MRI findings, thus further expanding the phenotypic spectrum of the glutaminyl-tRNA synthetase deficiency syndromes.
- Subjects :
- 0301 basic medicine
Microcephaly
030105 genetics & heredity
Biology
Amino Acyl-tRNA Synthetases
03 medical and health sciences
Cellular and Molecular Neuroscience
Epilepsy
Atrophy
Intellectual Disability
Intellectual disability
Genetics
medicine
Missense mutation
Humans
Child
Genetics (clinical)
Exome sequencing
Progressive microcephaly
Brain Diseases
Homozygote
Brain
Disease gene identification
medicine.disease
Phenotype
Mutation
Female
Subjects
Details
- ISSN :
- 13646753
- Volume :
- 18
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Neurogenetics
- Accession number :
- edsair.doi.dedup.....ef338b763aedb3dc368752baf283056a