Search

Background: This study investigates the serial mediation of self-esteem and smartphone dependency in the relationship between negative parenting style and adolescents’ aggression.Methods: We conducted a secondary data analysis of the 2018 Korean Children and Youth Panel Survey (KCYPS) and used the data of first-year middle school students. A mediation analysis was conducted using Hayes’ SPSS PROCESS Macro (Model 6).Results: The mediation of smartphone dependency was significant in the relationship between parents’ negative parenting style and aggression, but the mediation of self-esteem was not. Negative parenting style significantly affected adolescents’ aggression through the sequential mediation of self-esteem and smartphone dependency.Conclusions: Appropriate interventions should be prepared to help adolescents increase their self-esteem and reduce smartphone dependency, thus reducing the aggression that a negative parenting style induces.

Bioresorbable electroceuticals, as a therapeutic approach for peripheral neuropathy, hold substantial potential, given their capability of spontaneous degradation and elimination, thereby obviating the necessity for surgical removal. Recent advances in bioresorbable electronics provide significant progress with rational design strategies on materials and device structures, allowing for a wide range of clinical applications. Nonetheless, two major challenges must be addressed to enable their practical adaptation in medical settings. First, they require sustainable energy solutions with biodegradable components that can operate for prolonged periods through a biosafe powering mechanism. More importantly, their functionality is rarely trusted due to the unpredictable device lifetime, complicated by the complex degradation kinetics of polymers. We propose an on-demand bioresorbable neurostimulator to address these challenges, where clinical operations can be manipulated using biosafe ultrasound sources. The ultrasound-mediated transient mechanism enables: i) electrical stimulation through transcutaneous ultrasound-driven triboelectricity and ii) rapid device elimination using high-intensity ultrasound without adverse health consequences. Furthermore, our neurostimulator provides remarkable therapeutic benefits for both acquired peripheral nerve injury and hereditary peripheral neuropathy, as demonstrated through nerve conduction studies and histopathological analyses. Through this study, we anticipate that the on-demand bioresorbable neurostimulator will introduce a paradigm shift in medical implants to treat peripheral neuropathy.

Charcot-Marie-Tooth disease (CMT) and related diseases are a genetically and clinically heterogeneous group of peripheral neuropathies. Particularly, mutations in several aminoacyl-tRNA synthetase (ARS) genes have been reported to cause axonal CMT (CMT2) or distal hereditary motor neuropathy (dHMN). However, the common pathogenesis among CMT subtypes by different ARS gene defects is not well understood. This study was performed to investigate ARS gene mutations in a CMT cohort of 710 Korean families. Whole-exome sequencing was applied to 710 CMT patients who were negative for PMP22 duplication. We identified 12 disease-causing variants (from 13 families) in GARS1, AARS1, HARS1, WARS1, and YARS1 genes. Seven variants were determined to be novel. The frequency of overall ARS gene mutations was 1.22% among all independent patients diagnosed with CMT and 1.83% in patients negative for PMP22 duplication. WARS1 mutations have been reported to cause dHMN; however, in our patients with WARS1 variants, CMT was associated with sensory involvement. We analyzed genotype-phenotype correlations and expanded the phenotypic spectrum of patients with CMT possessing ARS gene variants. We also characterized clinical phenotypes according to ARS genes. This study will be useful for performing exact molecular and clinical diagnoses and providing reference data for other population studies.

Whole-genome sequencing is the most comprehensive form of next-generation sequencing method. We aimed to assess the additional diagnostic yield of whole-genome sequencing in patients with clinically diagnosed Charcot–Marie–Tooth disease when compared with whole-exome sequencing, which has not been reported in the literature. Whole-genome sequencing was performed on 72 families whose genetic cause of clinically diagnosed Charcot–Marie–Tooth disease was not revealed after the whole-exome sequencing and 17p12 duplication screening. Among the included families, 14 (19.4%) acquired genetic diagnoses that were compatible with their phenotypes. The most common factor that led to the additional diagnosis in the whole-genome sequencing was genotype-driven analysis (four families, 4/14), in which a wider range of genes, not limited to peripheral neuropathy-related genes, were analysed. Another four families acquired diagnosis due to the inherent advantage of whole-genome sequencing such as better coverage than the whole-exome sequencing (two families, 2/14), structural variants (one family, 1/14) and non-coding variants (one family, 1/14). In conclusion, an evident gain in diagnostic yield was obtained from whole-genome sequencing of the whole-exome sequencing-negative cases. A wide range of genes, not limited to inherited peripheral neuropathy-related genes, should be targeted during whole-genome sequencing.

Objective The current study examined the differential empathic capacity, post-traumatic symptoms, and coping strategies in healthcare workers (HCWs) according to the exposure of verbal or physical workplace violence (WPV).Methods Using online survey, a total of 422 HCWs employed at a training general hospital of South Korea participated and completed self-reporting questionnaires including the WPV questionnaire with coping strategy, the Jefferson Scale of Physician Empathy.Results Those who experienced either only verbal violence or both physical and verbal violence had lower Jefferson Scale of Physician Empathy scores (p

Since 2019, Coronavirus Disease (COVID-19) has changed the concept of systemic sclerosis caused by viral infectious diseases. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative organism of COVID-19, has infected more than 1.36 billion people in 188 countries, and nearly 2.29 million have died. Although we have rapidly developed vaccines against COVID-19, the struggle to treat COVID-19 patients who exhibit complicated multiple organ sclerosis has continued ever since. Studies have reported that preexisting liver disease in 3-8% of patients increases metabolic dysfunction and mortality by 4-6-fold in association with the severity of COVID-19. Moreover, both confirmed and cured COVID-19 patients have been reported to develop pulmonary fibrosis, which is often related to poor prognosis of the complications. Therefore, in the present study, we summarize the possible mechanisms underlying the development of hepatic and pulmonary fibrosis caused by SARS-CoV-2 infection, based on recently published data. Furthermore, since stem cell-based treatments have been developed as a novel approach to treat COVID-19 patients with Systemic Sclerosis (SS), we discuss the implementation of stem cell-based treatments as a powerful regenerative tool owing to their notable immunomodulatory and anti-fibrotic effects.

Background and purpose Charcot-Marie-Tooth (CMT) disease is the most common hereditary peripheral neuropathy. CMT type 1A (CMT1A) accounts for approximately 50% of CMT patients and is linked to PMP22 gene duplication. Histone deacetylase-6 (HDAC6) has pleiotropic effects, such as regulating lipid homeostasis and cellular stress. Although HDAC6 has been regarded as a promising drug target for neurodegenerative diseases, its inhibition has not yet been tested in CMT1A. Here we have tested the therapeutic potential of CKD-504, a clinical stage HDAC6 inhibitor, in a mouse model of CMT1A EXPERIMENTAL APPROACH: The potency and selectivity of CKD-504 was evaluated, using a HDAC enzyme panel assay and western blots. The therapeutic potential of CKD-504 was evaluated using behavioural testing and electrophysiological assessments in the C22 mouse model of CMT1A. PMP22 protein expression and aggregation were analysed in mesenchymal stem cell-derived Schwann cells from CMT1A patients and sciatic nerves from C22 mice. Key results The HDAC6 inhibitor, CKD-504, modulated molecular chaperon proteins such as HSP90 and HSP70, which are involved in the folding/refolding of proteins such as PMP22. CKD-504 treatment restored myelination in both mesenchymal stem cell-derived Schwann cells from CMT1A patients and sciatic nerves of C22 mice and improved the axonal integrity of the sciatic nerve, leading to behavioural, electrophysiological, and histological improvements in C22 mice. Conclusion and implications A novel HDAC6 inhibitor, CKD-504, has potent therapeutic efficacy for CMT1A.

Charcot-Marie-Tooth disease type 1C (CMT1C) is a rare subtype associated with LITAF gene mutations. Until now, only a few studies have reported the clinical features of CMT1C.This study was performed to find CMT1C patients with mutation of LITAF in a Korean CMT cohort and to characterize their clinical features.In total, 1,143 unrelated Korean families with CMT were enrolled in a cohort. We performed whole exome sequencing to identify LITAF mutations, and examined clinical phenotypes including electrophysiological and MRI features for the identified CMT1C patients.We identified 10 CMT1C patients from three unrelated families with p.G112S mutation in LITAF. The frequency of CMT1C among CMT1 patients was 0.59%, which is similar to reports from Western populations. CMT1C patients showed milder symptoms than CMT1A patients. The mean CMT neuropathy score version 2 was 7.7, and the mean functional disability scale was 1.0. Electrophysiological findings showed a conduction block in 22% of affected individuals. Lower extremity MRIs showed that the superficial posterior and anterolateral compartments of the calf were predominantly affected.We found a conduction block in Korean CMT1C patients with p.G112S mutation and first described the characteristic MRI findings of the lower extremities in patients with LITAF mutation. These findings will be helpful for genotype-phenotype correlation and will widen understanding about the clinical spectrum of CMT1C.

The microrchidia (MORC)-family CW-type zinc finger 2 (MORC2) gene is related to DNA repair, adipogenesis and epigenetic silencing via the human silencing hub (HUSH) complex. MORC2 missense mutation is known to cause peripheral neuropathy of Charcot-Marie-Tooth disease type 2 Z (CMT2Z). However, there have been reports of peripheral and central neuropathy in patients, and the disease has been co-categorized with developmental delay, impaired growth, dysmorphic facies and axonal neuropathy (DIGFAN). The etiology of MORC2 mutation-mediated neuropathy remains uncertain. Here, we established and analyzed Morc2a p.S87L mutant mice. Morc2a p.S87L mice displayed the clinical symptoms expected in human CMT2Z patients, such as axonal neuropathy and skeletal muscle weakness. Notably, we observed severe central neuropathy with cerebella ataxia, cognition disorder and motor neuron degeneration in the spinal cord, and this seemed to be evidence of DIGFAN. Morc2a p.S87L mice exhibited an accumulation of DNA damage in neuronal cells, followed by p53/cytochrome c/caspase 9/caspase 3-mediated apoptosis. This study presents a new mouse model of CMT2Z and DIGFAN with a Morc2a p.S87L mutation. We suggest that neuronal apoptosis is a possible target for therapeutic approach in MORC2 missense mutation. This article has an associated First Person interview with the first author of the paper., Summary: We present a new mouse model of Charcot-Marie-Tooth disease type 2 Z and developmental delay, impaired growth, dysmorphic facies and axonal neuropathy syndrome with a Morc2a p.S87L mutation, exhibiting peripheral and central neuronal apoptosis.

Distal hereditary motor neuropathies (dHMN) are a group of inherited peripheral nerve disorders characterized by length-dependent motor neuron weakness and subsequent muscle atrophy. Missense mutations in the gene encoding small heat shock protein HSPB1 (HSP27) have been associated with hereditary neuropathies including dHMN. HSPB1 is a member of the small heat shock protein (sHSP) family characterized by a highly conserved α-crystallin domain that is critical to their chaperone activity. In this study, we modeled HSPB1 mutant-induced neuropathies in Drosophila using a human HSPB1S135F mutant that has a missense mutation in its α-crystallin domain. Overexpression of the HSPB1 mutant produced no significant defect in the Drosophila development, however, a partial reduction in the life span was observed. Further, the HSPB1 mutant gene induced an obvious loss of motor activity when expressed in Drosophila neurons. Moreover, suppression of histone deacetylase 6 (HDAC6) expression, which has critical roles in HSPB1 mutant-induced axonal defects, successfully rescued the motor defects in the HSPB1 mutant Drosophila model.

Addressing the mental health needs of healthcare workers (HCWs), who are at high risk of suicide, is an important public health issue. Therefore, this systematic review investigated the effect of psychosocial intervention targeting suicidal behavior (i.e., suicidal ideation, attempt, or fulfillment) of HCWs. Five electronic databases were searched for interventional studies reporting HCWs’ suicidal behavior outcomes. Only two interventional studies were included in this review, and no consistent conclusion was drawn from the existing literature regarding the psychosocial prevention strategies focusing on the suicide risk of HCWs. The results indicate that compared with numerous observational studies reporting poor mental health and/or severity of suicidal risk among HCWs, intervention studies using psychosocial strategies to reduce the risk of suicide are relatively scarce. Although the insufficient number and heterogeneity of the included studies leave the results inconclusive, our findings emphasize the need to fill the research gap in this field. The causes of the gap are further explored, and suggestions for future research are provided.

This study aims to examine how work-to-life negative spillover is associated with depressive symptoms among working women and to explore moderating effect of social activities satisfaction on the relationship between work-to-life spillover and depression. This was a secondary data analysis from a sample of 2869 employed women from the 7th Korean Longitudinal Survey of Women and Families. The results showed that work-to-life negative spillover was positively associated with depressive symptoms. Additionally, there was a significant moderating effect of social activities satisfaction on the relationship between work-to-life negative spillover and depressive symptoms (β = 0.176, p < 0.05). It was found that the low social activity group showed fewer depressive symptoms induced by the negative work-to-life spillover than the high social activity group. Based on the results of our study, effective strategies and policies for work-family compatibility and interventions aimed at reducing the work induced stress and depressive symptoms are recommended.

Background Charcot‐Marie‐Tooth disease (CMT) is the most common disorder of inherited peripheral neuropathies characterized by distal muscle weakness and sensory loss. CMT is usually classified into three types, demyelinating, axonal, and intermediate neuropathies. Mutations in myelin protein zero (MPZ) gene which encodes a transmembrane protein of the Schwann cells as a major component of peripheral myelin have been reported to cause various type of CMT. Methods This study screened MPZ mutations in Korean CMT patients (1,121 families) by whole exome sequencing and targeted sequencing. Results We identified 22 pathogenic or likely pathogenic MPZ mutations in 36 families as the underlying cause of the CMT1B, CMTDID, or CMT2I subtypes. Among them, five mutations were novel. The frequency of CMT patients with the MPZ mutations was similar or slightly lower compared to other ethnic groups. Conclusions We showed that the median onset ages and clinical phenotypes varied by subtypes: the most severe in the CMT1B group, and the mildest in the CMT2I group. This study also observed a clear correlation that earlier onsets cause more severe symptoms. We believe that this study will provide useful reference data for genetic and clinical information on CMT patients with MPZ mutations in Korea., Mutations in myelin protein zero (MPZ) gene which encodes a transmembrane protein of the Schwann cells have been reported to cause various type of CMT.We identified 22 pathogenic or likely pathogenic MPZ mutations in 36 families as the underlying cause of the CMT1B, CMTDID, or CMT2I subtypes.The mean onset ages and clinical phenotypes varied by subtypes: the most severe in the CMT1B group, and the mildest in the CMT2I group.

Charcot‑Marie‑Tooth disease (CMT) is the most common inherited neurological disorder of the peripheral nervous system. The major subtype, CMT type 1A (CMT1A), accounts for ~40% of CMT cases and is characterized by distal muscle atrophy and gait disturbances. Short hairpin (sh) RNA sequences are potentially advantageous therapeutic tools for distal muscle atrophy‑induced gait disturbance. Therefore, the current study focused on the effects of an optimal shRNA injection using the myostatin (mstn) gene inhibition system. shLenti‑Mstn A demonstrated significant suppression of endogenous mstn gene expression (>40%) via RT‑qPCR following direct injection into the gastrocnemius and rectus femoris of the hind limb in C22 mice. The results also reported that shLenti‑Mstn A treatment increased muscle mass and size of the hind limbs compared with mock‑treated mice via measurement of the mass of injected muscles and magnetic resonance imaging study. Furthermore, electrophysiological measurement using a Nicolet Viking Quest device revealed significantly improved compound muscle action potential (CMAP) in shLenti‑Mstn A‑treated mice compared with the mock group (P

Small heat shock proteins (sHSPs) are ATP-independent chaperones that help correct the folding of denatured proteins and protect cells from stress. Mutations in HSPB1, HSPB8, and HSPB3 are implicated in inherited peripheral neuropathies (IPNs), such as Charcot-Marie-Tooth disease type 2 (CMT2) and distal hereditary motor neuropathies (dHMN). This study, using whole exome sequencing or targeted gene sequencing, identified 9 pathogenic or likely pathogenic variants in these three sHSP genes from 11 Korean IPN families. Most variants were located in the evolutionally well conserved α-crystallin domain, except for p.P182S and p.S187L in HSPB1. As an atypical case, a patient with dHMN2 showed two compound heterozygous variants of p.R127Q and p.Y142H in HSPB1, suggesting a putative case of recessive inheritance, which requires additional research to confirm. Three HSPB8 variants were located in the p.K141 residue, which seemed to be a mutational hot spot. There were no significant differences between patient groups, which divided by sHSP genes for clinical symptoms such as onset age, severity, and nerve conduction. Early-onset patients showed a tendency of slightly decreased sensory nerve conduction values compared with late-onset patients. As a first Korean IPN cohort study examining sHSP genes, these results will, we believe, be helpful for molecular diagnosis and care of patients with CMT2 and dHMN.

Charcot–Marie–Tooth disease type 1A (CMT1A) is caused by 1.5-fold increased dosage of the PMP22; however, onset age and severity vary considerably among patients. The exact reason behind these phenotypic heterogeneities has rarely been discovered yet. Because miRNAs are the key regulators of gene expression, we speculated that variants of miRNAs might be the genetic modifiers for CMT1A. This study noticed a common single nucleotide polymorphism (n.86T > C, rs2292832) in the miR-149 which was predicted to target several CMT causing genes including PMP22. The rs2292832 was located near the 3′ end of the precursor microRNA of the miR-149. We performed an association study between the rs2292832 polymorphism and clinical phenotypes of CMT1A in subjects consisting of 176 unrelated Korean CMT1A patients and 176 controls. From this study, we observed that rs2292832 was closely associated to the onset age and severity of CMT1A. Particularly, the TC and CC genotypes were significantly associated with late onset and mild symptom. Therefore, we suggest that the rs2292832 variant in the miR-149 is a potential candidate as a genetic modifier which affects the phenotypic heterogeneity of CMT1A. This study may provide the first evidence that polymorphism in the miR gene is associated with the CMT1A phenotype.

Heat shock protein B3 (HSPB3) gene encodes a small heat-shock protein 27-like protein which has a high sequence homology with HSPB1. A mutation in the HSPB3 was reported as the putative underlying cause of distal hereditary motor neuropathy 2C (dHMN2C) in 2010. We identified a heterozygous mutation (c.352T>C, p.Tyr118His) in the HSPB3 from a Charcot-Marie-Tooth disease type 2 (CMT2) family by the method of targeted next generation sequencing. The mutation was located in the well conserved alpha-crystalline domain, and several in silico predictions indicated a pathogenic effect of the mutation. Clinical and electrophysiological features of the patients indicated the axonal type of CMT. Clinical symptoms without sensory involvements were similar between the present family and the previous family. Mutations in the HSPB1 and HSPB8 genes have been reported to be relevant with both types of CMT2 and dHMN. Our findings will help in the molecular diagnosis of CMT2 by expanding the phenotypic range due to the HSPB3 mutations.

Mutations in the NEFH gene encoding the heavy neurofilament protein are usually associated with neuronal damage and susceptibility to amyotrophic lateral sclerosis (ALS). Recently, frameshift variants in NEFH (p.Asp1004Glnfs*58 and p.Pro1008Alafs*56) have been reported to be the underlying cause of axonal Charcot-Marie-Tooth disease type 2CC (CMT2CC). The frameshift mutation resulted in a stop loss and translation of a cryptic amyloidogenic element (CAE) encoded by the 3' untranslated region (UTR). This study also identified a de novo c.3015_3027dup frameshift mutation predicting p.Lys1010Glnfs*57 in NEFH from a CMT2 family with an atypical clinical symptom of prominent proximal weakness. This mutation is located near the previously reported frameshift mutations, suggesting a mutational hotspot. Lower limb magnetic resonance imaging (MRI) revealed marked hyperintense signal changes in the thigh muscles compared with those in the calf muscles. Therefore, this study suggests that the stop loss and translational elongations by the 3' UTR of the NEFH mutations may be a relatively frequent genetic cause of axonal peripheral neuropathy with the specific characteristics of proximal dominant weakness.

Alanyl-tRNA synthetase 1 (AARS1) gene encodes a ubiquitously expressed class II enzyme that catalyzes the attachment of alanine to the cognate tRNA. AARS1 mutations are frequently responsible for autosomal dominant Charcot-Marie-Tooth disease type 2N (CMT2N). To identify pathogenic mutation in the Korean patients with CMT and distal hereditary motor neuronopathy (dHMN). We screened AARS1 mutations in 373 unrelated CMT families including 318 axonal CMT, 36 dHMN, and 19 intermediate CMT (Int-CMT) who were negative for 17p12 (PMP22) duplication or deletion using whole exome sequencing and targeted sequencing of CMT-related genes. This study identified an early onset Int-CMT family harboring an AARS1 p.Arg329His mutation which was previously reported as pathogenic in French and Australian families. The mutation was located in the highly conserved tRNA binding domain and several in silico analyses suggested pathogenic prediction of the mutations. The patients harboring p.Arg329His showed clinically similar phenotypes of the early onset and electrophysiological intermediate type as those in Australian patients with same mutation. We also found a novel c.2564A>G (p.Gln855Arg) in a CMT2 patient, but its’ pathogenic role was uncertain (variant of uncertain significance). This study suggests that the frequency of the AARS1 mutations appears to be quite low in Korean CMT. This is the first report of the AARS1 mutation in Korean CMT patients and will be helpful for the exact molecular diagnosis and treatment of Int-CMT patients.

OBJECTIVE This study aimed to investigate how work-life balance (WLB) corresponds to cognitive functions and which mental health conditions play a mediating role in this association among Korean bus drivers. METHODS The cognitive failures questionnaire (CFQ) was administered to 347 bus drivers in Seoul, Korea. The differences in the CFQ and WLB scores were examined by analysis of covariance, and a structural equation model (SEM) was constructed for investigating the mediating role of mental health indices between WLB and CFQ scores. RESULTS Compared with the highest subjective work-life balance group, the lowest group had significantly higher CFQ scores. In the SEM, anxiety was a mediating variable between subjective work-life balance and CFQ scores. CONCLUSIONS Work-life balance is associated with cognitive failures among Korean bus drivers, and anxiety was a key mediating mental health indicator.

Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive neuropathy caused by SH3TC2 mutations, characterized by spine deformities and cranial nerve involvement. This study identified four CMT4C families with compound heterozygous SH3TC2 mutations from 504 Korean demyelinating or intermediate CMT patients. The frequency of the CMT4C was calculated as 0.79% in demyelinating and intermediate patients (n = 504), but it was calculated as 2.02% in patients without PMP22 duplication (n = 198). The CMT4C frequency was similar to patients in Japan, but it was relatively low compared to those patients in other populations. The symptom was less severe and slowly progressed compared to the other AR-CMT. A patient harboring an intermediate neuropathy showed cranial nerve involvement but did not have scoliosis. This study will be helpful in making molecular diagnoses of demyelinating or intermediate CMT due to SH3TC2 mutations.

Objective Myelinated Schwann cells (SCs) in adult peripheral nerves dedifferentiate into immature cells in demyelinating neuropathies and Wallerian degeneration. This plastic SC change is actively involved in the myelin destruction and clearance as demyelinating SCs (DSCs). In inherited demyelinating neuropathy, pathologically differentiated and dysmyelinated SCs constitute the main nerve pathology. Methods We investigated whether this SC plastic status in human neuropathic nerves could be determined by patient sera to develop disease‐relevant serum biomarkers. Based on proteomics analysis of the secreted exosomes from immature SCs, we traced p75 neurotrophin receptor (p75) and neural cell adhesion molecule 1 (NCAM) in the sera of patients with peripheral neuropathy. Results Enzyme‐linked immunosorbent assay (ELISA) revealed that p75 and NCAM were subtype‐specifically expressed in the sera of patients with peripheral neuropathy. In conjunction with these ELISA data, pathological analyses of animal models and human specimens suggested that the presence of DSCs in inflammatory neuropathy and of supernumerary nonmyelinating or dysmyelinating SCs in inherited neuropathy could potentially be distinguished by comparing the expression profiles of p75 and NCAM. Interpretation This study indicates that the identification of disease‐specific pathological SC stages might be a valuable tool for differential diagnosis of peripheral neuropathies.

Mutations in the Dynactin 1 (DCTN1) gene have been demonstrated to result in various neurodegenerative diseases, including distal hereditary motor neuropathy type 7B (dHMN7B), Perry syndrome, amyotrophic lateral sclerosis and amyotrophic lateral sclerosis‑frontotemporal dementia. However, since the first dHMN7B patient with a DCTN1 mutation was described in 2003, to the best of our knowledge no further cases have been reported. In the present study, the DCTN1 p.G59S mutation was identified in two unrelated families from a total of 24 Korean families with dHMN, by whole exome sequencing. Codon 59 appears to be the mutational hot spot in the DCTN1 gene, as all described dHMN7B patients to date have harbored an identical p.G59S mutation. The families of the present study with the DCTN1 mutation had a milder disease with a later onset compared with the previously described patients. No affected family members exhibited facial muscle weakness or bulbar involvement. One family member demonstrated vocal cord palsy as the initial sign of disease; however, in the other family hand muscle weakness was the first major symptom. No affected patients demonstrated sensory loss or upper motor neuron involvements. Although this is only the second report of dHMN7B resulting from a DCTN1 mutation, the frequency of the DCTN1 mutation was not low in the Korean population examined, and clinical heterogeneities were observed in patients with the DCTN1 mutation. Therefore, it may be beneficial to screen all dHMN patients for the DCTN1 mutation.

Background and purpose Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) are known to cause Charcot-Marie-Tooth disease (CMT). These mutations are very rare in most countries, but not in certain Mediterranean countries. The purpose of this study was to identify the clinical and neuroimaging characteristics of Korean CMT patients with GDAP1 mutations. Methods Gene sequencing was applied to 1,143 families in whom CMT had been diagnosed from 2005 to 2020. PMP22 duplication was found in 344 families, and whole-exome sequencing was performed in 699 patients. Magnetic resonance imaging (MRI) were obtained using either a 1.5-T or 3.0-T MRI system. Results We found ten patients from eight families with GDAP1 mutations: five with autosomal dominant (AD) CMT type 2K (three families with p.R120W and two families with p.Q218E) and three with autosomal recessive (AR) intermediate CMT type A (two families with homozygous p.H256R and one family with p.P111H and p.V219G mutations). The frequency was about 1.0% exclusive of the PMP22 duplication, which is similar to that in other Asian countries. There were clinical differences among AD GDAP1 patients according to mutation sites. Surprisingly, fat infiltrations evident in lower-limb MRI differed between AD and AR patients. The posterior-compartment muscles in the calf were affected early and predominantly in AD patients, whereas AR patients showed fat infiltration predominantly in the anterolateral-compartment muscles. Conclusions This is the first cohort report on Korean patients with GDAP1 mutations. The patients with AD and AR inheritance routes exhibited different clinical and neuroimaging features in the lower extremities. We believe that these results will help to expand the knowledge of the clinical, genetic, and neuroimaging features of CMT.

Analysis of large numbers of single-nucleotide polymorphisms (SNPs) can increase individual discrimination power, and, particularly, it can supply important evidence for kinship or ethnic identification. We identified 300 Korean-specific SNPs from 306 Korean whole-exome sequencing (WES) data. Functionally significant SNPs (variants in splicing site, missense, nonsense, and exonic indels) were filtered out from the variant pool, and SNPs with minor allele frequencies (MAFs) of0.3 in the 1000 Genomes (1000G) database but0.3 in the Korean population were selected. Genotypes obtained from WES were confirmed by the Sanger sequencing method. The identified markers were evenly distributed throughout the autosomal chromosomes. All the SNPs were in the Hardy-Weinberg equilibrium with a mean MAF of 0.415 (0.161 in 1000G). The mean heterozygosities were 0.476 (observed) and 0.470 (experimental). The combined power of discrimination was very high. Korean MAFs in most SNPs were similar to those for the Chinese and Japanese populations, but were significantly higher than those for several other ethnic populations. These selected SNPs will be used to develop forensic markers and are expected to be widely used for additional individual identification, ethnic discrimination, and linkage analysis for kinship tests.

Charcot–Marie–Tooth disease (CMT) is a group of clinically and genetically heterogeneous peripheral neuropathies. We identified two axonal CMT type 2F (CMT2F) families presented with distally predominant weakness in upper and lower extremities with sensory involvement. This study identified a c.404C>T (p.Ser135Phe) mutation in HSPB1 gene as the underlying cause of the both families by applying of whole exome sequencing. The p.Ser135Phe mutation was completely cosegregated with the affected members in the both families, and it was not found in 300 healthy controls. This mutation has been previously reported as the causes of CMT2F or hereditary motor neuropathy 2B (dHMN2B). The mutation was located in the highly conserved alpha-crystallin domain, and several in silico analyses also predicted that the mutation is likely to be pathogenic. HSPB1 encodes heat shock protein 27 (HSP27) which belongs to the superfamily of small stress induced proteins. These results suggest that the HSPB1 mutation is underlying cause of CMT2F phenotype shown in the present families. We believe that this study will be useful for the molecular diagnosis of peripheral neuropathies.

Mutations in the inverted formin-2 (INF2) gene were recently identified in patients with autosomal dominant intermediate Charcot-Marie-Tooth (DI-CMT) disease and focal segmental glomerulosclerosis (FSGS). Here, we identified a novel p.L132P INF2 mutation in a Korean family with DI-CMT and FSGS by whole-exome sequencing. This mutation was cosegregated with affected individuals in the family and was not found in the 300 controls. The two affected members exhibited juvenile onset sensorimotor polyneuropathy and FSGS. Nerve conduction studies showed an intermediate range of motor nerve conduction velocities. We report a novel INF2 mutation in a family with DI-CMT and FSGS as the first case in Koreans. The INF2 mutation appears to be a major cause of CMT with FSGS.

Immune damages on the peripheral myelin sheath under pro-inflammatory milieu result in primary demyelination in inflammatory demyelinating neuropathy. Inflammatory cytokines implicating in the pathogenesis of inflammatory demyelinating neuropathy have been used for the development of potential biomarkers for the diagnosis of the diseases. In this study, we have found that macrophages, which induce demyelination, expressed a B-cell-recruiting factor CXC chemokine ligand 13 (CXCL13) in mouse and human inflammatory demyelinating nerves. The serum levels of CXCL13 were also higher in inflammatory demyelinating neuropathic patients but not in acute motor axonal neuropathy or a hereditary demyelinating neuropathy, Charcot-Marie-Tooth disease type 1a. In addition, CXCL13-expressing macrophages were not observed in the sciatic nerves after axonal injury, which causes the activation of innate immunity and Wallerian demyelination. Our findings indicate that the detection of serum CXCL13 will be useful to specifically recognize inflammatory demyelinating neuropathies in human.

In this paper, we study the extent to which the pecking order theory of capital structure provides a satisfactory account of the financing behavior of Korean fisheries firms using financing deficit. The major results of this study are as follows. Firstly, we find that the financing deficit is a important factor that explains the pecking order theory of fisheries firms`capital structure. However, the financing deficit does not wipe out the effects of conventional variables. The information in the financing deficit appears to be factored in along with many other things that fisheries firms take into account. Such result is consistent with the result of Frank and Goyal(2003). Secondly, we find that profitability is only one factor explaining the capital structure of fisheries firms among conventional variables when we test the regression of leverage with financing deficit during post IMF period. This result is different from the previous researches of Korean fisheries firms. (Kang and Jeong; 1997, Nam, Lee, and Hong; 2011) Finally, we examine the dynamics of capital structure of Korean fisheries firms firstly. It will allow a more detailed analysis for capital structure determinants for Korean fisheries firms.

Aim: To determine the pregnancy termination rate, and perinatal and 1-year infant mortality rates following prenatally-detected congenital heart disease (CHD) and trends over an 11-year period. Methods: Between 1994 and 2005, 1603 gravidas underwent fetal echocardiography in our institution, in which 378 fetuses were diagnosed with CHD. The study period was divided into the following three groups for time-trend analysis: 1994–1997, 1998–2001, and 2002–2005. Data regarding gestational age at diagnosis and delivery, the presence of extracardiac or chromosomal abnormalities, pregnancy termination rate, and perinatal and 1-year mortalities were collected by review of medical records and telephone interviews. Results: Among 378 fetuses with a prenatally-detected CHD, complete perinatal and infant outcomes were available for 336 fetuses (88.9%). There was a gradual increase in prenatally-detected CHD by fetal echocardiography during the study period (1994–1997, 10.3%; 1998–2001, 17.3%; and 2002–2005, 24.3%). The mean gestational ages at diagnosis and delivery were 27.2 ± 5.6 and 37.8 ± 2.9 weeks, respectively. Overall, the pregnancy termination rate in this study population was 20.2% and the perinatal and 1-year infant mortality rates were 6.3% and 9.7%, respectively. Among the fetuses who underwent cardiac surgery, surgical mortality occurred in two (3.8%); both died more than 1 month after surgery. Although the pregnancy termination rates remained unchanged, there was a significant decrease in perinatal and 1-year infant mortality rates over the study period. Conclusion: Although the perinatal and 1-year infant mortalities following prenatally-detected CHD have continued to decrease significantly during the past 11 years, pregnancy termination rates have remained unchanged.

We deposited ZnO thin films at room temperature by RF magnetron sputtering method with home-made targets, and for application tests using these films as transparent conductive oxide (TCO) anodes, wet-chemical etching behaviors of ZnO films were also investigated using various chemicals. In order to fabricate ZnO-based OLED devices, various etchants such as HCl, HNO3, H2SO4 and H3PO4 have been studies for the wet etching of ZnO thin film. In this experiment, we introduced two new different chemicals as etchants, ferric chloride (FeCl3 ∙ 6H2O) and oxalic acid (C2H2O4) which were controlled with various concentrations in ZnO etching process and showed an anisotropy etching shape of ZnO films.

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and is a genetically and clinically heterogeneous disorder. We examined a Korean family in which two individuals had an autosomal-dominant axonal CMT with early-onset, sensory ataxia, tremor, and slow disease progression. Pedigree analysis and exome sequencing identified a de novo missense mutation (p.Y223H) in the diacylglycerol O-acyltransferase 2 (DGAT2) gene. DGAT2 encodes an endoplasmic reticulum-mitochondrial-associated membrane protein, acyl-CoA:diacylglycerol acyltransferase, which catalyzes the final step of the triglyceride (TG) biosynthesis pathway. The patient showed consistently decreased serum TG levels, and overexpression of the mutant DGAT2 significantly inhibited the proliferation of mouse motor neuron cells. Moreover, the variant form of human DGAT2 inhibited the axonal branching in the peripheral nervous system of zebrafish. We suggest that mutation of DGAT2 is the novel underlying cause of an autosomal-dominant axonal CMT2 neuropathy. This study will help provide a better understanding of the pathophysiology of axonal CMT and contribute to the molecular diagnostics of peripheral neuropathies.

Hereditary sensory and autonomic neuropathy type I (HSAN I) is an autosomal dominant disease characterized by prominent sensory impairment, resulting in foot ulcers or amputations and has a juvenile to adult onset. The major underlying causes of HSAN I are mutations in SPTLC1, which encodes the first subunit of serine palmitoyltransferase (SPT). To date, there have been no reports with regard to an HSAN patient of Korean origin. In this report we discussed an HSAN I patient with a missense mutation in SPTLC1 (c.992C>T: p.S331F). The patient had noticed frequent falls, lower leg weakness and hand tremors at age five. The patient also presented with foot ulcers, muscle hypotrophy, cataracts, hoarseness, vocal cord palsy and respiratory difficulties and succumbed to the condition at the age of 28 years. In accordance with previous reports, a mutation in Ser331 in the present patient was associated with early-onset and a severe phenotype. Therefore, Ser331 in SPTLC1 is a crucial amino acid, which characterizes the HSAN I phenotype.

Objective: To identify the genetic cause of an autosomal recessive demyelinating Charcot-Marie-Tooth disease type 4B (CMT4B) family. Methods: We enrolled 14 members of a Korean family in which 3 individuals had demyelinating CMT4B phenotype and obtained distal sural nerve biopsies from all affected participants. We conducted exome sequencing on 6 samples (3 affected and 3 unaffected individuals). Results: One pair of heterozygous missense mutations in the SET binding factor 1 ( SBF1 ) gene (22q13.33), also called MTMR5 , was identified as the underlying cause of the CMT4B family illness. Clinical phenotypes of affected study participants with CMT4B were similar, to some extent, to patients with CMT4B1 and CMT4B2. We found a similar loss of large myelinated fibers and focally folded myelin sheaths in our patients, but the actual number of myelinated fibers was different from CMT4B1 and CMT4B2. Conclusions: We suggest that the compound heterozygous mutations in SBF1 are the underlying causes of a novel CMT4B subtype, designated as CMT4B3. We believe that this study will lead to mechanistic studies to discover the function of SBF1 and to the development of molecular diagnostics for CMT disease.

To determine the pregnancy termination rate, and perinatal and 1-year infant mortality rates following prenatally-detected congenital heart disease (CHD) and trends over an 11-year period.Between 1994 and 2005, 1603 gravidas underwent fetal echocardiography in our institution, in which 378 fetuses were diagnosed with CHD. The study period was divided into the following three groups for time-trend analysis: 1994-1997, 1998-2001, and 2002-2005. Data regarding gestational age at diagnosis and delivery, the presence of extracardiac or chromosomal abnormalities, pregnancy termination rate, and perinatal and 1-year mortalities were collected by review of medical records and telephone interviews.Among 378 fetuses with a prenatally-detected CHD, complete perinatal and infant outcomes were available for 336 fetuses (88.9%). There was a gradual increase in prenatally-detected CHD by fetal echocardiography during the study period (1994-1997, 10.3%; 1998-2001, 17.3%; and 2002-2005, 24.3%). The mean gestational ages at diagnosis and delivery were 27.2 +/- 5.6 and 37.8 +/- 2.9 weeks, respectively. Overall, the pregnancy termination rate in this study population was 20.2% and the perinatal and 1-year infant mortality rates were 6.3% and 9.7%, respectively. Among the fetuses who underwent cardiac surgery, surgical mortality occurred in two (3.8%); both died more than 1 month after surgery. Although the pregnancy termination rates remained unchanged, there was a significant decrease in perinatal and 1-year infant mortality rates over the study period.Although the perinatal and 1-year infant mortalities following prenatally-detected CHD have continued to decrease significantly during the past 11 years, pregnancy termination rates have remained unchanged.

Background Mutations in the gene encoding periaxin (PRX) are known to cause autosomal recessive Dejerine-Sottas neuropathy (DSN) or Charcot-Marie-Tooth disease type 4F. However, there have been no reports describing Korean patients with these mutations. Case report We examined a Korean DSN patient with an early-onset, slowly progressive, demyelinating neuropathy with prominent sensory involvement. Whole-exome sequencing and subsequent capillary sequencing revealed novel compound heterozygous nonsense mutations (p.R392X and p.R679X) in PRX. One mutation was transmitted from each of the patient's parents. No unaffected family member had both mutations, and the mutations were not found in healthy controls. Conclusions We believe that these novel compound heterozygous nonsense mutations are the underlying cause of DSN. The clinical, electrophysiologic, and pathologic phenotypes in this family were similar to those described previously for patients with PRX mutations. We have identified the first PRX mutation in a Korean patient with DSN.

Background X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is caused by mutations in the gene encoding phosphoribosyl pyrophosphate synthetase I (PRPS1). There has been only one case report of CMTX5 patients. The aim of this study was to identify the causative gene in a family with CMTX with peripheral neuropathy and deafness. Case Report A Korean family with X-linked recessive CMT was enrolled. The age at the onset of hearing loss of the male proband was 5 months, and that of steppage gait was 6 years; he underwent cochlear surgery at the age of 12 years. In contrast to what was reported for the first patients with CMTX5, this patient did not exhibit optic atrophy. Furthermore, there was no cognitive impairment, respiratory dysfunction, or visual disturbance. Assessment of his family history revealed two male relatives with very similar clinical manifestations. Electrophysiological evaluations disclosed sensorineural hearing loss and peripheral neuropathy. Whole-exome sequencing identified a novel p.Ala121Gly (c.362C>G) PRPS1 mutation as the underlying genetic cause of the clinical phenotype. Conclusions A novel mutation of PRPS1 was identified in a CMTX5 family in which the proband had a phenotype of peripheral neuropathy with early-onset hearing loss, but no optic atrophy. The findings of this study will expand the clinical spectrum of X-linked recessive CMT and will be useful for the molecular diagnosis of clinically heterogeneous peripheral neuropathies.

632 Background: Understanding recent advances of tumor biology allow us to divide breast cancer (BC) into at least five subtypes. Different therapeutic approaches are needed based on these molecula...

e11053 Background: Gene expression profiles using DNA microarrays have shown at least 5 distinct breast cancer (BC) subtypes. According to these subtypes, clinical features can vary in relapse patt...

e21081 Background: Activation of the EGFR signaling can lead to the activation of MAPK, PI3K/AKT, the STAT pathway resulting in tumor growth, inhibition of apoptosis, cell migration and invasion. Tumor cells that over-express both EGFR and HER2, exhibit aggressive tumor cell growth, owing to the increased potential for EGFR/HER2 heterodimerization and signaling. HER2 overexpression has been found to correlate with a worse prognosis in breast cancer. However, the clinical significance of EGFR status in the HER2 positive early breast cancer remains to be evaluated. Methods: This study aims to evaluate EGFR status and its clinical impact in HER2 positive in early breast cancer. To address this issue, biomarker evaluation was performed using immunohistochemistry to semiquantitate estrogen (ER), progesterone (PR), HER2, and EGFR expression in the large cohort of cases with early breast cancers. Amplification of HER2 was confirmed by fluorescent in situ hybridization. Results: HER2 overexpression was found in 2...

5524 Background: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma o...