Publications of the week – GABRB3, SLC2A1, and SCN1A

No novel genes. This was actually a slow week with respect to publications in epilepsy genetics. No new gene was published, so we’ll focus on three publications that tell us bit more about three genes that we already know. This week’s publications cover new reports on GABRB3, SLC2A1, and SCN1A in brain malformations.

Confocal microscopy of mouse brain by Zeiss microscropy (under a Creative Commons licence from

Confocal microscopy of mouse brain by Zeiss microscropy (under a Creative Commons licence from

GABRB3 visualized. De novo mutations in GABRB3 have recently been identified to cause epileptic encephalopathies. In their recent publication in Nature, Miller and Ariescu present the first crystal structure of the GABRB3 protein, the first crystal structure of a human GABA receptor, and suggest that benzamidine might constitute a novel modulator.
Crystallography makes it possible to get a close-up view of how mutations affect protein structure – this may lead to ideas about possible novel drugs.

Glut1 in epilepsy and migraine. In a recent case report in Neuropediatrics, Ragona and collaborators identify a novel de novo mutation in SLC2A1, coding for Glut1. The patient had refractory absence epilepsy starting at age 4, microcephaly, and migraine. Seizures became worse with fasting.
Conclusion: This case report is a good reminder that atypical absence epilepsies may be due to Glut1 deficiency, even though the age of onset is later than in the early absence epilepsies.

SCN1A and brain malformation. In a recent publication in Epilepsia, Barba and collaborators identify six patients with Dravet Syndrome due to mutations in SCN1A and co-occurring brain malformations including periventricular nodular heterotopia and focal cortical dysplasia. They point out that both SCN1A mutations and brain malformations can co-exist in patients, suggesting that these patients may not be ideal candidates for epilepsy surgery due to a bad post-operative outcome.
Conclusion: The question of how genetic information should be included into the presurgical decision-making process is becoming increasingly important. There is much to learn.

Ingo Helbig

Child Neurology Fellow and epilepsy genetics researcher at the Children’s Hospital of Philadelphia (CHOP), USA and Department of Neuropediatrics, Kiel, Germany

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