Mutations in the P/Q type calcium channel CACNA1A have been implicated in epileptic encephalopathy, familial hemiplegic migraine, episodic ataxia 2, and spinocerebellar ataxia 6, but not Rett syndrome.
Using whole exome sequencing we found a de novo heterozygous, missense mutation of FHF1 (p.Arg52His, NM_004113), a mutation that has been very recently described in 7 patients with an early onset epileptic encephalopathy.
While classically thought to act at sodium channels, lamotrigine also modulates the activity of the P/Q-type calcium channel, making it a candidate for precision therapy for patients with epileptic encephalopathy due to CACNA1A pathogenic variants.
To delineate the phenotype of early childhood epileptic encephalopathy due to de novo mutations of CHD2, which encodes the chromodomain helicase DNA binding protein 2.
Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic encephalopathies due to other gene mutations.
We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have an identifiable causal de novo mutation.
We conclude that the GABRA1 (R214C) variant reduces channel activity and surface expression of mutant receptors, thereby contributing to the pathogenesis of genetic EE.