HCN2 is a top candidate gene for absence epilepsy, in fact there are few genes that are higher on the list of candidates than HCN2, which is expressed in the thalamus, modulating thalamocortical oscillations.  The problem is that mutations in humans have not been described to date, an orphan candidate gene in a way…

This paper presents another line of evidence for the involvement of HCN2 in absence epilepsy. A spontaneous mouse mutant -apathetic- was found to have a 4 base pair insertion in the coding region of HCN2.  Ingo

This 2009 blog post has been transferred to the EuroEPINOMICS blog from www.epilepsygenetics.net.

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Helbig, I. HCN2 goes apathetic. Retrieved [enter date], from http://www.euroepinomics.wordpress.com

This paper is featured since it deals with the basics of epilepsy genetics – investigating whether a phenotype has a genetic contribution by looking at familial aggregation.  The authors investigate patients with neuro-cysticercosis and do not find evidence for familial aggregation.

Whereas the methodology is straightforward, it remains unclear what effect the authors could exclude.  For example, one would not expect a large degree of familial aggregation in herpes simplex encephalitis, but mutations in TLR3 and UNC-93B can be identified in some patients.

Ingo

This 2009 blog post has been transferred to the EuroEPINOMICS blog from www.epilepsygenetics.net.

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Helbig, I. The genetics of seizures in neurocysticercosis. Retrieved [enter date], from http://www.euroepinomics.wordpress.com

This gene continues to be a mystery.  An epilepsy gene not expressed in neurons with no obvious link to ion channels.

EFHC1 is one of the few genes found in human epilepsies that has been replicated in several studies.  The predominant phenotype of patients carrying EFHC1 variant is Juvenile Myoclonic Epilepy, where also familial inheritance is observed.  However, EFHC1 mutations have also been found in cases of other IGE subtypes and cryptogenic Temporal Lobe Epilepsy (TLE).

Suzuki et al. now report on their findings in EFHC1-deficient mice. The animals develop spontaneous myoclonus and are susceptible to seizures.  Interestingly, the authors find that EFHC1 is not expressed in neuron, but only in the choroid plexus and postnatal ependymal cilia.  In addition, GABAergic neurons are not affected.

The question remains how EFHC1 can lead to an idiopathic epilepsy phenotype that is assumed to be a disease of ion channels. Or maybe not?

Ingo

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Helbig, I. EFHC1-deficient mice develop myoclonic seizures. Retrieved [enter date], from http://www.euroepinomics.wordpress.com

SV2A variants and variants in related genes are not associated with the response to Levetiracetam in a sufficiently large cohort.

Ingo

This 2009 blog post has been transferred to the EuroEPINOMICS blog from www.epilepsygenetics.net.

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Helbig, I. Response to LEV and lack of SV2A variants. Retrieved [enter date], from http://www.euroepinomics.wordpress.com

This paper by Bahi-Buisson et al. describes a family with Myoclonic Absence Epilepsy with Photosensitivity and the hyperinsulinism/hyperammonemia (HI/HA) syndrome and mutations in the glutamate dehydrogenase (GDH) gene.

Is this IGE-like phenotype a metabolic disorder rather than a channelopathy?

Ingo

This 2009 blog post has been transferred to the EuroEPINOMICS blog from www.epilepsygenetics.net.

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Helbig, I. GDH mutations in a Myoclonic absence Epilepsy. Retrieved [enter date], from http://www.euroepinomics.wordpress.com

In this paper in Annals, the author report on nine patients with folinic-acid responsive seizures with mutations in antiquitin (ALDH7A1), which was previously only associated with pyridoxine-dependent seizures.

Folinic acid responsive seizures are a cause of neonatal epilepsy and characteristic peaks of unidentified compounds are observed on chromatography of the cerebrospinal fluid that sets this condition apart from other neonatal epilepsies. Now this condition is found to be allelic with pyridoxine-dependent seizures with a number of implications for diagnosis and treatment.

Ingo

This 2009 blog post has been transferred to the EuroEPINOMICS blog from www.epilepsygenetics.net.

Please quote this blog (APA format) as

Helbig, I. Antiquitin mutations in folinic-acid responsive seizures. Retrieved [enter date], from http://www.euroepinomics.wordpress.com

In this review, Saul Mullen and Ingrid Scheffer review the phenotypes and animal models for epilepsies associated with SCN1A mutations. This review will finally coin the term interneuronopathy for the various diseases with SCN1A mutations and is an additional reference for Severe Infantile Multifocal Epilepsy (SIMFE) beside the 2007 Harkin paper, which is freely available online.

Ingo

This 2009 blog post has been transferred to the EuroEPINOMICS blog fromwww.epilepsygenetics.net.

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Helbig, I. Review: SCN1A in men and mice. Retrieved [enter date], from http://www.euroepinomics.wordpress.com

This 2009 blog post has been transferred to the EuroEPINOMICS blog from www.epilepsygenetics.net.

The first paper of 2009 for this blog is a publication from our own consortium.  We describe the first microdeletion that predisposes to Idiopathic Generalised Epilepsy that is found in 1% of patients with IGE.  The same microdeletion had been identified previously in various neurodevelopmental disorders including schizophrenia, autism and intellectual disability. http://1.usa.gov/npuzk4

Ingo

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Helbig, I. 15q13.3 microdeletions in IGE. Retrieved [enter date], from http://www.euroepinomics.wordpress.com