SCN1A – This is what you need to know in 2014

Update. As information on the epilepsies caused by SCN1A mutations are amongst our most frequently read posts, we thought that a quick update on the state-of-the art regarding SCN1A would be timely. These are the ten things about SCN1A that you should known in 2014. Continue reading

The OMIM epileptic encephalopathy genes – a 2014 review

EIEE1-19. Online Mendelian Inheritance in Man (OMIM) is one of the most frequently accessed online databases for information on genetic disorders. Genes for epileptic encephalopathies are organized within a phenotypic series entitled Early Infantile Epileptic Encephalopathy (EIEE). The EIEE phenotypic series currently lists 19 genes (EIEE1-19). Let’s review the evidence for these genes as of 2014. Continue reading

SLC25A22, migrating seizures and mitochrondial glutamate deficiency

MPSI. Migrating partial seizures of infancy (MPSI) are a catastrophic form of infantile epilepsy that was entirely unexplained until de novo mutations in KCNT1 were identified in a subset of sporadic cases in 2012. For familial MPSI, however, the genetic basis remained unknown. In a recent publication in Annals of Neurology, Poduri and collaborators identify mutations in SCL25A22 in a family with recessive MPSI. Their study sheds light on the genetic basis of catastrophic epilepsies and the phenotypic range of mitochondrial glutamate starvation. Continue reading

QARS mutations, tRNA, and neurodegeneration with migrating seizures

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

A new spectrum unfolding – KCNT1 mutations in ADNFLE and MMPSI

A surprising finding. The genetic basis of many epileptic encephalopathies and familial epilepsies remains unknown. Novel sequencing technologies such as Next Generation Sequencing now offer the possibility to identify the genetic basis of these conditions. However, it is a rare event that a single gene is implicated in two completely different epilepsy subtypes. Such a finding has now been reported in Nature Genetics. The KCNT1 gene is found to be mutated in Malignant Migrating Partial Seizures of Infancy (MMPSI) and a severe form of Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE). I doublechecked at least three times whether both papers actually talk about the same gene. Continue reading