CHD2 variants are a risk factor for photosensitivity in epilepsy
نویسندگان
چکیده
Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. 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 determined whether CHD2 variation underlies photosensitivity in common epilepsies, specific photosensitive epilepsies and individuals with photosensitivity without seizures. We studied 580 individuals with epilepsy and either photosensitive seizures or abnormal photoparoxysmal response on electroencephalography, or both, and 55 individuals with photoparoxysmal response but no seizures. We compared CHD2 sequence data to publicly available data from 34 427 individuals, not enriched for epilepsy. We investigated the role of unique variants seen only once in the entire data set. We sought CHD2 variants in 238 exomes from familial genetic generalized epilepsies, and in other public exome data sets. We identified 11 unique variants in the 580 individuals with photosensitive epilepsies and 128 unique variants in the 34 427 controls: unique CHD2 variation is over-represented in cases overall (P = 2.17 × 10(-5)). Among epilepsy syndromes, there was over-representation of unique CHD2 variants (3/36 cases) in the archetypal photosensitive epilepsy syndrome, eyelid myoclonia with absences (P = 3.50 × 10(-4)). CHD2 variation was not over-represented in photoparoxysmal response without seizures. Zebrafish larvae with chd2 knockdown were tested for photosensitivity. Chd2 knockdown markedly enhanced mild innate zebrafish larval photosensitivity. CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome, eyelid myoclonia with absences. Unique CHD2 variants are also associated with photosensitivity in common epilepsies. CHD2 does not encode an ion channel, opening new avenues for research into human cortical excitability.
منابع مشابه
Photosensitivity and CHD2 Variants
Investigators from multinational institutions hypothesized that disruption of CHD2, which encodes chromodomain helicase DNA-binding protein 2, would be associated with common forms of photosensitive epilepsy or photosensitivity manifesting as a photoparoxysmal response alone.
متن کاملCHD2 myoclonic encephalopathy is frequently associated with self-induced seizures.
OBJECTIVE 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. METHODS We analyzed the medical history, MRI, and video-EEG recordings of 9 individuals with de novo CHD2 mutations and one with a de novo 15q26 deletion encompassing CHD2. RESULTS Seizures began at a mean of 26 mon...
متن کاملAbsence epilepsy and the CHD2 gene: an adolescent male with moderate intellectual disability, short-lasting psychoses, and an interstitial deletion in 15q26.1–q26.2
Deletions of the 15q26 region encompassing the chromodomain helicase DNA binding domain 2 (CHD2) gene have been associated with intellectual disability, behavioral problems, and several types of epilepsy. Including the cases mentioned in ECARUCA (European cytogeneticists association register of unbalanced chromosome aberrations) and DECIPHER (database of genomic variation and phenotype in human...
متن کاملRelation of photosensitivity to epileptic syndromes.
Photosensitivity is the most common mode of seizure precipitation. It is age-related, more frequent in females, and most often found in generalised epilepsies. Little is known about its relation to individual epileptic syndromes. This study on 1062 epileptic patients who had 4007 split screen video EEG investigations revealed that the relation to generalised epilepsy is even more close than gen...
متن کامل“Selfie-epilepsy”: A novel photosensitivity
PURPOSE Photosensitivity is a well-described phenomenon; affecting a relatively small proportion of individuals with epilepsy. Typically people with photosensitive epilepsies are at risk of seizures induced by shimmering natural light, strobe lights and with particular patterns or flicker frequencies on television and video games. METHODS & RESULTS We present a novel case of photosensitivity ...
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عنوان ژورنال:
دوره 138 شماره
صفحات -
تاریخ انتشار 2015