Breakpoint analysis for cytogenetically balanced translocation revealed unexpected complex structural abnormalities and suggested the position effect for MEF2C.

Many disease-causing genes have been identified by determining the breakpoints of balanced chromosomal translocations. Recent progress in genomic analysis has accelerated the analysis of chromosomal translocation-breakpoints at the nucleotide level. Using a long-read whole-genome sequence, we analyzed the breakpoints of the cytogenetically balanced chromosomal translocation t(5;15)(q21;26.3), which was confirmed to be of de novo origin, in a patient with a neurodevelopmental disorder. The results showed complex rearrangements with seven fragments consisting of five breakpoint-junctions (BJs). Four of the five BJs showed microhomologies of 1-3-bp, and only one BJ displayed a signature of blunt-end ligation, indicating chromothripsis as the underlying mechanism. Although the BJs did not disrupt any disease-causing gene, the clinical features of the patient were compatible with MEF2C haploinsufficiency syndrome. Complex rearrangements were located approximately 2.5-Mb downstream of MEF2C. Therefore, position effects were considered the mechanism of the occurrence of MEF2C haploinsufficiency syndrome.

A Case of Acute Encephalopathy Associated with Acute Focal Bacterial Nephritis.

Acute encephalopathy is a syndrome characterized by an acute onset of disturbance of consciousness. Many acute encephalopathies are caused by viral infections; however, they can also be a result of bacterial infections. Acute focal bacterial nephritis (AFBN) can cause neurological symptoms, such as irritation, unconsciousness, and seizures. In some cases, AFBN-associated acute encephalopathy has also been reported. This report describes the first case of acute encephalopathy with AFBN without significant findings on brain MRI. The patient was a 3-year-old male, who had two episodes of febrile seizures at the ages of 1 and 2 years. He developed disturbance of consciousness, irritability, excitability, and neck stiffness on the day after admission. There were no abnormal findings on brain MRI; however, a generalized high-voltage slow wave was noted on electroencephalography (EEG). His urinary sediment count was elevated, and Morganella morganii and Enterococcus faecalis were detected in the urinary culture. A diagnosis of acute encephalopathy with urinary tract infection (UTI) was made. Intravenous (IV) antibiotics were administered to treat the UTI, while methylprednisolone pulse therapy and IV immunoglobulin were administered to treat acute encephalopathy. Additionally, AFBN was detected in both kidneys on contrast-enhanced CT. The patient received a second course of methylprednisolone pulse therapy due to the persistent high voltage slow wave noted on the EEG on day 8. Furthermore, contrast-enhanced CT revealed AFBN in both kidneys. The final diagnosis was acute encephalopathy with AFBN; however, we had initially diagnosed febrile seizures associated with UTI. It should be noted that acute encephalopathy is associated with AFBN.

Mutation in the STXBP1 Gene Associated with Early Onset West Syndrome: A Case Report and Literature Review.

Syntaxin-binding protein1 (STXBP1) is a member of the Sec1/Munc18-1 protein family, which comprises important regulators of the secretory and synaptic vesicle fusion machinery underlying hormonal and neuronal transmission, respectively. STXBP1 pathogenic variants are associated with multiple neurological disorders. Herein, we present the case of a Japanese girl with a mutation in the STXBP1 gene, who was born at 40 weeks without neonatal asphyxia. At 15 days old, she developed epilepsy and generalized seizures. Around 88 days old, she presented with a series of nodding spasms, with the seizure frequency gradually increasing. Interictal EEG indicated hypsarrhythmia and she presented with developmental regression. At 1.5 years old, genetic testing was performed and mutational analysis revealed an STXBP1 gene mutation (c.875G > A: p.Arg292His). Accordingly, she was diagnosed with developmental and epileptic encephalopathy, presenting West syndrome's clinical characteristics caused by the STXBP1 gene mutation. Although drug treatment has reduced the frequency of epileptic seizures, her development has remained regressive. The relationship between the location and type of genetic abnormality and the phenotype remains unclear. Future studies should investigate the genotype−phenotype correlation and the underlying pathophysiology to elucidate the causal relationships among the multiple phenotype-determining factors.

Recurrent de novo pathogenic variant of WASF1 in a Japanese patient with neurodevelopmental disorder with absent language and variable seizures.

A recurrent de novo pathogenic variant of WASF1, NM_003931:c.1516C>T [p.Arg506*], was identified in a 6-year-old female Japanese patient with severe developmental delay, hypotonia, hyperkinetic behavior, and distinctive facial features. The initial report of five adult patients with WASF1 variants was the only previous report regarding variants of this gene; this is the second such report, reaffirming that rare but recurrent truncating variants of WASF1 are associated with severe neurodevelopmental disorders.

Effect of anti-attention-deficit hyperactivity disorder (ADHD) medication on clinical seizures and sleep EEG: A retrospective study of Japanese children with ADHD.

AIMS: Patients with attention-deficit hyperactivity disorder (ADHD) often exhibit basic or paroxysmal wave abnormalities on electroencephalography (EEG). Methylphenidate (MPH), an anti-ADHD stimulant, has been reported to lower the seizure threshold. However, there have been no reports comparing EEG changes before and after administration of the central nervous system (CNS) stimulant MPH, or atomoxetine (ATX) hydrochloride, a non-CNS stimulant. In this study, we investigated changes in sleep EEG before and after the administration of ADHD treatment drugs. METHOD: With the approval of the ethics committee, the medical records of 28 children with ADHD (23 men and 5 women) who gave consent were retrospectively investigated. The appearance of sudden abnormal waves during a 10-minute sleep EEG recording was measured in 0.1-second units, and the duration of these waves was calculated as the paroxysmal index (PI). RESULTS: Paroxysmal index did not differ significantly between patients who received MPH and those who received ATX. In addition, there were no exacerbations of clinical seizures. CONCLUSION: It was concluded that ADHD medications do not have an adverse effect on epileptic seizures or abnormal sleep EEGs.

A Web-Based Auditory and Visual Emotion Perception Task Experiment With Children and a Comparison of Lab Data and Web Data.

Due to the COVID-19 pandemic, the significance of online research has been rising in the field of psychology. However, online experiments with child participants are rare compared to those with adults. In this study, we investigated the validity of web-based experiments with child participants 4-12 years old and adult participants. They performed simple emotional perception tasks in an experiment designed and conducted on the Gorilla Experiment Builder platform. After short communication with each participant via Zoom videoconferencing software, participants performed the auditory task (judging emotion from vocal expression) and the visual task (judging emotion from facial expression). The data collected were compared with data collected in our previous similar laboratory experiment, and similar tendencies were found. For the auditory task in particular, we replicated differences in accuracy perceiving vocal expressions between age groups and also found the same native language advantage. Furthermore, we discuss the possibility of using online cognitive studies for future developmental studies.

Audiovisual emotion perception develops differently from audiovisual phoneme perception during childhood.

This study investigated the developmental paths in the use of audiovisual information for the perception of emotions and phonemes by Japanese speakers. Children aged 5 to 12 years and adults aged 30 to 39 years engaged in an emotion perception task in which speakers expressed their emotions through their faces and voices, and a phoneme perception task using phonemic information in speakers' lip movements and speech sounds. Results indicated that Japanese children's judgement of emotions by using auditory information increased with increasing age, whereas the use of audiovisual information for judging phonemes remained constant with increasing age. Moreover, adults were affected by visual information more than children. We discuss whether these differences in developmental patterns are due to differential integration processes for information indicative of emotions and phonemes, as well as possible cultural / linguistic reasons for these differences.

Clinical features of early myoclonic encephalopathy caused by a CDKL5 mutation.

BACKGROUND: CDKL5 deficiency is caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene and clinically manifests often in females as drug-resistant intractable epilepsy and severe psychomotor retardation. CASE REPORT: We report the case of a girl with a CDKL5 mutation born at 39 weeks without neonatal asphyxia. She developed epilepsy at age 1 month with myoclonus of the face and limbs, and non-rhythmic and irregular opsoclonus. She developed tonic seizures and epileptic spasms at 6 months of age and was diagnosed with symptomatic West syndrome and underwent adrenocorticotropic hormone therapy but her seizures were refractory. At the age of 4, she was introduced to our hospital and development was at 2 months of age. We diagnosed her with early myoclonic encephalopathy (EME) due to the remaining suppression-burst pattern observed on an electroencephalogram and her symptoms since onset were mainly myoclonus. At 14 years of age, mutational analysis revealed a CDKL5 mutation (c.380A > G:p.His127Arg). She was diagnosed with epileptic encephalopathy exhibiting clinical features of early myoclonic epilepsy caused by CDKL5 deficiency. CONCLUSIONS: Early onset epilepsy with severe psychomotor retardation without a known etiology may be caused by a mutation in CDKL5. More research investigating a genotype-phenotype correlation of CDKL5 mutations is necessary because clinical severity may be associated with the location and type of mutations.

Neurobehavioral and hemodynamic evaluation of Stroop and reverse Stroop interference in children with attention-deficit/hyperactivity disorder.

Failure of executive function (EF) is a core symptom of attention-deficit/hyperactivity disorder (ADHD). However, various results have been reported and sufficient evidence is lacking. In the present study, we evaluated the characteristics of children with ADHD using the Stroop task (ST) and reverse Stroop task (RST) that reflects the inhibition function of EF. We compared children with ADHD, typically developing children (TDC), and children with autism spectrum disorder (ASD), which is more difficult to discriminate from ADHD. A total of 10 children diagnosed with ADHD, 15 TDC, and 11 children diagnosed with ASD, all matched by age, sex, language ability, and intelligence quotient, participated in this study. While each subject performed computer-based ST and RST with a touch panel, changes in oxygenated hemoglobin (oxy-Hb) were measured in the prefrontal cortex (PFC) by near-infrared spectroscopy (NIRS) to correlate test performance with neural activity. Behavioral performance significantly differed among 3 groups during RST but not during ST. The ADHD group showed greater color interference than the TDC group. In addition, there was a negative correlation between right lateral PFC (LPFC) activity and the severity of attention deficit. Children with ADHD exhibit several problems associated with inhibition of color, and this symptom is affected by low activities of the right LPFC. In addition, it is suggested that low hemodynamic activities in this area are correlated with ADHD.

Altered brain activity for phonological manipulation in dyslexic Japanese children.

Because of unique linguistic characteristics, the prevalence rate of developmental dyslexia is relatively low in the Japanese language. Paradoxically, Japanese children have serious difficulty analysing phonological processes when they have dyslexia. Neurobiological deficits in Japanese dyslexia remain unclear and need to be identified, and may lead to better understanding of the commonality and diversity in the disorder among different linguistic systems. The present study investigated brain activity that underlies deficits in phonological awareness in Japanese dyslexic children using functional magnetic resonance imaging. We developed and conducted a phonological manipulation task to extract phonological processing skills and to minimize the influence of auditory working memory on healthy adults, typically developing children, and dyslexic children. Current experiments revealed that several brain regions participated in manipulating the phonological information including left inferior and middle frontal gyrus, left superior temporal gyrus, and bilateral basal ganglia. Moreover, dyslexic children showed altered activity in two brain regions. They showed hyperactivity in the basal ganglia compared with the two other groups, which reflects inefficient phonological processing. Hypoactivity in the left superior temporal gyrus was also found, suggesting difficulty in composing and processing phonological information. The altered brain activity shares similarity with those of dyslexic children in countries speaking alphabetical languages, but disparity also occurs between these two populations. These are initial findings concerning the neurobiological impairments in dyslexic Japanese children.

High-yield production of scutellaria radix flavonoids (baicalein, baicalin and wogonin) by liquid-culture of Scutellaria baicalensis root-derived cells

Production of baicalein, baicalin and wogonin by liquid culture of Scutellaria baicalensis cells derived from the plant root was studied. The maximum production obtained were 119 mg/L of baicalein at two week, 1372 mg/L of baicalin at eight week, and 14 mg/L of wogonin at two week. In addition, the production of baicalin was drastically increased to 1000 mg/L level at 3-week culture, and the extremely high production rate (339 mg/L•week) was obtained. In the comparison of total antioxidative activities among baicalein, baicalin and wogonin, evaluated by thiocyanate method, it was suggested that the location of hydroxyl groups both at 5- and 6-position contributed to enhancement of radical scavenging activity, and/or methoxylation at 8-position diminished the activity. The possibility of utilizing these flavonoids for natural antioxidants and medicine is also discussed.

Difference of growth-inhibitory effect of Scutellaria baicalensis-producing flavonoid wogonin among human cancer cells and normal diploid cell.

Methanol extract from cultured Scutellaria baicalensis cells inhibited the proliferation of human monocytic leukemia cell line THP-1 and human osteogenic sarcoma cell line HOS. The inhibitory effects of baicalin, baicalein and wogonin, the three major flavonoids contained in the extract, were studied. It should be noted that wogonin did not show the inhibitory effect on human fetal lung normal diploid cell line TIG-1, as compared to the inhibition observed in cancer cells. Physiological analyses in THP-1 cells showed that wogonin induced cell cycle arrest at G(2)/M phase and apoptosis. This is the first report discovering a cancer-specific apoptosis-inducing activity of wogonin.