Ryo Sato

Two cases of early-onset myoclonic seizures with continuous parietal delta activity caused by EEF1A2 mutations.

BACKGROUND Mutations in the elongation factor 1 alpha 2 (EEF1A2) gene have recently been shown to cause severe intellectual disability with early-onset epilepsy. The specific manifestations of mutations in this gene remain unknown. CASE REPORT We report two cases of severe intellectual disability accompanied by early-onset epilepsy with continuous delta activity evident on electroencephalography. Both cases presented with developmental delay and repetitive myoclonic seizures in early infancy. Both cases showed continuous high-voltage delta activity over both parietal areas when awake, as revealed by interictal electroencephalograms. After the emergence of continuous delta activity, development stagnated. One case showed some development after relief of the seizures and epileptic activity, but drug resistant seizures recurred, and the development again became stagnant. In both cases, a de novo recurrent heterozygous mutation in EEF1A2 [c.364G>A (p.E122K)] was identified by whole-exome sequencing. CONCLUSION This report provides clinical data on epileptic encephalopathy in patients with EEF1A2 mutation. Continuous high-voltage delta activity seen over both parietal areas may be a unique manifestation of EEF1A2 mutation. Epileptic activity may aggravate the effect of the mutation on brain development.

The molecular and phenotypic spectrum of IQSEC2-related epilepsy.

IQSEC2 is an X‐linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants.

Novel biallelic mutations in the PNPT1 gene encoding a mitochondrial-RNA-import protein PNPase cause delayed myelination

Recent studies suggest that impaired transcription or mitochondrial translation of small RNAs can cause abnormal myelination. A polynucleotide phosphorylase (PNPase) encoded by PNPT1 facilitates the import of small RNAs into mitochondria. PNPT1 mutations have been reported in patients with neurodevelopmental diseases with mitochondrial dysfunction. We report here 2 siblings with PNPT1 mutations who presented delayed myelination as well as mitochondrial dysfunction. We identified compound heterozygous mutations (c.227G>A; p.Gly76Asp and c.574C>T; p.Arg192*) in PNPT1 by quartet whole‐exome sequencing. Analyses of skin fibroblasts from the patient showed that PNPase expression was markedly decreased and that import of the small RNA RNaseP into mitochondria was impaired. Exogenous expression of wild‐type PNPT1, but not mutants, rescued ATP production in patient skin fibroblasts, suggesting the pathogenicity of the identified mutations. Our cases expand the phenotypic spectrum of PNPT1 mutations that can cause delayed myelination.

Neuroepidemiology of Porencephaly, Schizencephaly, and Hydranencephaly in Miyagi Prefecture, Japan

BACKGROUND No population-based surveys of porencephaly, schizencephaly, and hydranencephaly have been conducted in Japan or other Asian countries. We performed a neuroepidemiologic analysis to elucidate the incidence of porencephaly, schizencephaly, and hydranencephaly in Miyagi prefecture, Japan, during 2007-2011. METHODS We sent inquiry forms in February 2012 to three neonatal intensive care units, 25 divisions of orthopedic surgery in municipal hospitals, 33 divisions of pediatrics including one university hospital, municipal hospitals, pediatric practitioners, and institutions for physically handicapped children located in Miyagi prefecture. These covered all clinics related to pediatric neurology and orthopedic surgery in Miyagi prefecture. In the inquiry, diagnostic criteria for porencephaly, schizencephaly, and hydranencephaly were described and representative images of magnetic resonance imaging were shown. We obtained an 82% (27 of 33) response rate from the divisions of pediatrics, a 100% (3 of 3) response rate from the neonatal intensive care units, and a 68% (17 of 25) response rate from orthopedic surgery clinics. The magnetic resonance imaging scans of each patient were retrieved and inspected. RESULTS Five, one, and two individuals developed porencephaly, schizencephaly, and hydranencephaly, respectively. The estimated incidence rates of porencephaly, schizencephaly, and hydranencephaly were 5.2 (95% confidence interval [CI], 0.6-9.8), 1.0 (95% CI, 0.0-3.1), and 2.1 (95% CI, 0.0-5.0) per 100,000 live births, respectively. CONCLUSIONS The prevalence rates of porencephaly, schizencephaly, and hydranencephaly at birth reported herein are compatible with results reported previously in the United States and European countries. The overall prevalence rate of these three diseases was 8.3 (95% CI, 2.6-14.1) per 100,000 live births.

Phenytoin-responsive epileptic encephalopathy with a tandem duplication involving FGF12.

Nonsecreting fibroblast growth factors (FGFs), which are sodium channel–binding proteins, have recently been associated with neurodevelopmental disorders,1,2 similar to some voltage-gated sodium channel subunits. Recently, a de novo mutation in FGF12 (p.R52H) was reported in a pair of siblings with epileptic encephalopathies.3 The affected siblings developed severe seizures within 1 month of age, and their seizures were refractory to multiple antiepileptic drugs. This mutation has a gain-of-function effect on sodium channel gating, which might lead to increased neuronal excitability. Here, we report another case of FGF12-related epileptic encephalopathy. In contrast to the previous report, the phenotype in our patient was relatively mild. Of note, his seizures responded to phenytoin, a sodium channel blocker, similar to epileptic encephalopathy associated with SCN2A4 and SCN8A,5 encoding voltage-gated sodium channel subunits.

A case of new PCDH12 gene variants presented as dyskinetic cerebral palsy with epilepsy

Here we report a Japanese patient with new compound heterozygous truncating variants in the PCDH12 gene. As compared to the previously reported families who had congenital microcephaly, intrauterine growth retardation, intracranial calcification, and neonatal seizure associated with dysplasia of the midbrain-hypothalamus-optic tract, the present patient showed no midbrain-hypothalamus dysplasia or congenital/postnatal microcephaly, but dyskinetic cerebral palsy and severe intellectual disability as well as multifocal epilepsy. To understand phenotypic spectrum associated with PCDH12 variants, more reports are needed.

Ultrasound source using a rectangular vibrating plate combined with rigid walls

Ultrasound sources that use a stripe-mode rectangular vibrating plate radiate strong ultrasound waves in the air. In this study, we investigated the design strategy for combining the vibrating plate with rigid walls and evaluated the intense ultrasound waves radiated by the sound source. First, we examined the design method for a rectangular transverse vibrating plate with both ends fixed and the vibration amplitude distribution of the vibrating plate. Second, we measured the sound pressure distribution in the formation of the standing wave field. Finally, we clarified the relationship between the input power and sound pressure of the standing wave field antinodes.

A Theoretical Study of Initial Deposition Processes of Mg on MgO: A Novel Quantum Chemical Molecular Dynamics Approach

Initial deposition processes of Mg on MgO were studied using our novel quantum chemical molecular dynamics (QCMD) simulator. This novel simulator was developed on the basis of our tight-binding quantum chemical molecular dynamics (TB-QCMD) simulator and our molecular dynamics simulator. The justification of the novel QCMD simulator was shown by the excellent agreement of the QCMD result with the first-principles results and experimental results for the physicochemical properties of the MgO crystal. Dynamic behaviors of Mg atom deposited on the MgO(001) and (111) surfaces were simulated by the novel QCMD method. It was shown that the mobility of Mg deposited on the MgO(001) surface was larger than that on the (111) surface, which suggests the difference between the interaction of the deposited Mg atom with the MgO(111) surface and that with the MgO(001) surface.

Interhole correlation and phase separation in t-J model

Interhole and interelectron correlations as well as a transition to phase separation in the t-J model near half filling are reconsidered using a variational Monte Carlo method. As a trial wave function, we use a state that can simultaneously represent a d-wave superconducting and antiferromagnetic (AF) orders and allows for nearest-neighbor hole-hole and spin-spin correlation factors and band renormalization effects. It is found that a transition occurs at J = J PS ~ 2.5t for the doping rates δ = 0.08 and 0.20 from a seemingly uniform state to phase separation (J > J PS) of singly occupied sites and empty sites. For J < J PS, where the values used for cuprate superconductors (0.25 J/t 0.5) are included, the interhole correlation is always repulsive. This result is negative to an intuitive picture for cuprates: Two holons coherently move in the background of AF orders.

Two Japanese cases of epileptic encephalopathy associated with an FGF12 mutation

A heterozygous mutation in the fibroblast growth factor 12 (FGF12) gene, which elevates the voltage dependence of neuronal sodium channel fast inactivation, was recently identified in some patients with epileptic encephalopathy. Here we report 1 Japanese patient diagnosed with early infantile epileptic encephalopathy (EIEE) and another diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). These 2 patients had an identical heterozygous missense mutation [c.341G>A:p.(Arg114His)] in FGF12 , which was identified with whole-exome sequencing. This mutation is identical to previously reported mutations in cases with early onset epileptic encephalopathy. One of our cases exhibited EIMFS, and this case responded to phenytoin and high-dose phenobarbital (PB). FGF12-related epileptic encephalopathy may exhibit diverse phenotypes and may respond to sodium channel blockers or high-dose PB.