Q for glutamine. Transfer RNAs (tRNAs) are small adaptor molecules that match a nucleotide sequence to a given amino acid during protein translation. After unloading their amino acid payload, tRNAs are recharged with new amino acids through specific tRNA synthetases. Q is the official letter for the amino acid glutamine, and its respective tRNA synthetase is glutaminyl-tRNA synthetase (QARS). In a recent publication in the American Journal of Human Genetics, Zhang and colleagues identify compound heterozygous mutations in the QARS gene in two families with progressive microcephaly, neurodegeneration, and intractable, early-onset epilepsy. Interestingly, in at least two probands, the seizures are described as migrating partial seizures reminiscent of Malignant Migrating Partial Seizures of Infancy (MMPSI) due to mutations in KCNT1. The disease mechanism, however, appears to be entirely different. Continue reading
Tag Archives: pontocerebellar hypoplasia
CASK aberrations in Ohtahara syndrome
Suppression-burst. Ohtahara Syndrome is a rare epileptic encephalopathy with onset in the first weeks of life. The typical EEG feature of Ohtahara Syndrome is suppression-burst activity, suggesting a profound disruption of cerebral function. Ohtahara Syndrome can be caused by severe brain malformations and neurometabolic disorders. In addition, mutations in ARX and STXBP1 are known causes of Ohtahara Syndrome. In a recent publication in Epilepsia, genetic alterations in CASK were identified in patients with Ohtahara Syndrome and cerebellar hypoplasia. Given that CASK mutations are the known cause for a complex X-chromosomal disorder, this report provides us with an interesting example of what happens when genes underlying distinct clinical dysmorphology syndromes cross over to the epilepsies. Continue reading
