This report describes epilepsy, familial adult myoclonic, 4, an autosomal dominant adult-onset myoclonic epilepsy. The human gene implicated is YEATS2, which encodes YEATS domain containing 2, a scaffolding subunit of the ADA2A-containing histone acetyltransferase complex. There is one high-scoring fly ortholog, Dmel\D12, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Human YEATS2 has not been introduced into flies.
Neuronally-targeted RNAi-mediated knockdown of Dmel\D12 results in seizure-like behavior in larvae in response to electrical shock and thermal stress, including delayed recovery after electrical or thermal stress. Adult flies exhibit a similar response to mechanical stress. Both larvae and adult flies exhibit locomotor defects. Ubiquitous RNAi-mediated knockdown significantly reduces the lifespan of adult flies, but is not lethal.
[updated Apr. 2024 by FlyBase; FBrf0222196]
Progressive myoclonic epilepsy (PME) is characterized by the presence of both muscle contractions (myoclonus) and seizures (epilepsy). Myoclonus occurs separately from seizures; the two types of symptoms respond differently to the same drugs and may evolve differently during the course of the disease. Myoclonus is frequently a greater problem than seizures, because it less amenable to control by available drugs. [from NORD, Progressive Myoclonus Epilepsy; 2024.04.01]
[EPILEPSY, FAMILIAL ADULT MYOCLONIC, 4; FAME4](https://omim.org/entry/615127)
[YEATS DOMAIN-CONTAINING PROTEIN 2; YEATS2](https://omim.org/entry/613373)
Thirteen individuals in a 3 generation Thai family had adult-onset cortical tremor, 7 of whom also had generalized seizures. The average age of onset was 19.5 years (range 10-33) for tremor and 25 years (range 19-33) for seizures. Only 1 patient had onset of seizures before tremor. The seizures were well-controlled, and none of the patients had cognitive impairment. Electrophysiologic studies confirmed the cortical origin of the myoclonus in most patients. Among 10 patients with EEG studies, 9 had spike and wave or polyspike and wave discharges, and 7 had multifocal discharges that corresponded with contralateral jerky movement and photosensitivity. Seven patients had increased amplitudes of cortical somatosensory evoked potentials, and all had the C-reflex. Two patients showed premyoclonic cortical discharges detected by jerk-locked back averaging. (Yeetong et al. 2013, pubmed:22713812) [from MIM:615127; 2024.04.01]
Familial adult myoclonic epilepsy-4 (FAME4) is caused by a heterozygous 5-bp repeat expansion, (TTTCA)n, in intron 1 of the YEATS2 gene (613373) on chromosome 3q26.32-q28. One such family has been reported. [from MIM:615127; 2024.04.01]
YEATS2 is a scaffolding subunit of the ADA2A (TADA2A)-containing (ATAC) histone acetyltransferase complex (Wang et al., 2008, pubmed:18838386). [from MIM:613373; 2024.04.01]
One to one (1 human to 1 Drosophila); YEATS2 has one high-scoring Drosophila ortholog, D12.
High-scoring ortholog of human YEATS2 (1 Drosophila to 1 human).
