anticodon and Microcephaly

anticodon has been researched along with Microcephaly* in 2 studies

Other Studies

2 other study(ies) available for anticodon and Microcephaly

Article	Year
Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy. Nature communications, 2019, 02-12, Volume: 10, Issue:1 Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes. Topics: Alleles; Anticodon; Child; Child, Preschool; Disease Progression; Epilepsy; Exome Sequencing; Female; Genetic Predisposition to Disease; Humans; Longitudinal Studies; Loss of Function Mutation; Male; Microcephaly; Models, Molecular; Mutation; Neurodevelopmental Disorders; Pedigree; Protein Biosynthesis; Protein Interaction Domains and Motifs; RNA, Transfer; Valine-tRNA Ligase; Whole Genome Sequencing	2019
Expansion of the QARS deficiency phenotype with report of a family with isolated supratentorial brain abnormalities. Neurogenetics, 2015, Volume: 16, Issue:2 We describe a family with QARS deficiency due to compound heterozygous QARS mutations, including c.1387G > A (p.R463*) in the catalytic core domain and c.2226C > G (p.Q742H) in the anticodon domain, both previously unreported and predicted damaging. The phenotype of the male index further confirms this specific aminoacyl-transfer RNA (tRNA) synthetase disorder as a novel genetic cause of progressive microcephaly with diffuse cerebral atrophy, severely deficient myelination, intractable seizures, and developmental arrest. However, in contrast to the two hitherto published families, the cerebellum and its myelination are not affected. An awareness that QARS mutations may cause isolated supratentorial changes is crucial for properly directing genetic analysis. Topics: Amino Acyl-tRNA Synthetases; Anticodon; Brain; Child; Family; Genetic Predisposition to Disease; Humans; Magnetic Resonance Imaging; Male; Microcephaly; Mutation; Phenotype	2015

Article

Year

Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.

Nature communications, 2019, 02-12, Volume: 10, Issue:1

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes.

Topics: Alleles; Anticodon; Child; Child, Preschool; Disease Progression; Epilepsy; Exome Sequencing; Female; Genetic Predisposition to Disease; Humans; Longitudinal Studies; Loss of Function Mutation; Male; Microcephaly; Models, Molecular; Mutation; Neurodevelopmental Disorders; Pedigree; Protein Biosynthesis; Protein Interaction Domains and Motifs; RNA, Transfer; Valine-tRNA Ligase; Whole Genome Sequencing

2019

Expansion of the QARS deficiency phenotype with report of a family with isolated supratentorial brain abnormalities.

Neurogenetics, 2015, Volume: 16, Issue:2

We describe a family with QARS deficiency due to compound heterozygous QARS mutations, including c.1387G > A (p.R463*) in the catalytic core domain and c.2226C > G (p.Q742H) in the anticodon domain, both previously unreported and predicted damaging. The phenotype of the male index further confirms this specific aminoacyl-transfer RNA (tRNA) synthetase disorder as a novel genetic cause of progressive microcephaly with diffuse cerebral atrophy, severely deficient myelination, intractable seizures, and developmental arrest. However, in contrast to the two hitherto published families, the cerebellum and its myelination are not affected. An awareness that QARS mutations may cause isolated supratentorial changes is crucial for properly directing genetic analysis.

Topics: Amino Acyl-tRNA Synthetases; Anticodon; Brain; Child; Family; Genetic Predisposition to Disease; Humans; Magnetic Resonance Imaging; Male; Microcephaly; Mutation; Phenotype

2015