The Effects of a Gate Bias Condition on 1.2 kV SiC MOSFETs during Irradiating Gamma-Radiation.

We investigated the effects of gate bias regarding the degradation of electrical characteristics during gamma irradiation. Moreover, we observed the punch through failure of 1.2 kV rated commercial Silicon Carbide (SiC) Metal Oxide Semiconductor Field Effect Transistors (MOSFETs) due to the influence of gate bias. In addition, the threshold voltage (VT) and on-resistance (Ron) of the SiC MOSFETs decreased significantly by the influence of gate bias during gamma irradiation. We extracted the concentration of carriers and fixed charge (QF) in oxide using N-type SiC MOS capacitors and Transmission Line Measurement (TLM) patterns to analyze the effects of gamma irradiation. The Total Ionizing Dose (TID) effect caused by high-energy gamma-ray irradiation resulted in an increase in the concentration of holes and QF in both SiC and oxide. To analyze the phenomenon for increment of hole concentration in the device under gate bias, we extracted the subthreshold swing of SiC MOSFETs and verified the origin of TID effects accelerated by the gate bias. The QF and doping concentration of p-well values extracted from the experiments were used in TCAD simulations (version 2022.03) of the planar SiC MOSFET. As a result of analyzing the energy band diagram at the channel region of 1.2 kV SiC MOSFETs, it was verified that punch-through can occur in 1.2 kV SiC MOSFETs when the gate bias is applied, as the TID effect is accelerated by the gate bias.

Mild Clinical Features and Histopathologically Atypical Cores in Two Korean Families with Central Core Disease Harboring RYR1 Mutations at the C-Terminal Region.

BACKGROUND: Central core disease (CCD) is a congenital myopathy characterized by distinctive cores in muscle fibers. Mutations in the gene encoding ryanodine receptor 1 (RYR1) have been identified in most CCD patients. CASE REPORT: Two unrelated patients presented with slowly progressive or nonprogressive proximal muscle weakness since childhood. Their family history revealed some members with the same clinical problem. Histological analysis of muscle biopsy samples revealed numerous peripheral cores in the muscle fibers. RYR1 sequence analysis disclosed a novel mutation in exon 101 (c.14590T>C) and confirmed a previously reported mutation in exon 102 (c.14678G>A). CONCLUSIONS: We report herein two families with CCD in whom missense mutations at the C-terminal of RYR1 were identified. Although it has been accepted that such mutations are usually associated with a severe clinical phenotype and clearly demarcated central cores, our patients exhibited a mild clinical phenotype without facial muscle involvement and skeletal deformities, and atypical cores in their muscle biopsy specimens.

Limb-girdle myasthenia with tubular aggregates associated with novel GFPT1 mutations.

INTRODUCTION: Limb-girdle myasthenia with tubular aggregates (LGM with TAs) is a subtype of congenital myasthenic syndrome caused by recessive mutations of glutamine-fructose-6-phosphate transaminase 1 (GFPT1). METHODS: Clinical and neurophysiological assessment was made in a Korean boy who had proximal limb muscle weakness. Findings suggested a diagnosis of congenital myasthenic syndrome. RESULTS: Muscle biopsy disclosed numerous TAs in muscle fibers, and DNA sequence analysis disclosed 2 novel missense mutations (p.E256Q and p.M499T) in GFPT1. Treatment with oral cholinesterase inhibitors produced a dramatic improvement in muscle strength. CONCLUSIONS: GFPT1 is the key enzyme in the hexosamine biosynthesis pathway, and mutations in GFPT1 cause defective glycosylation in the proteins of the neuromuscular junction. Identification of LGM with TAs among patients with congenital myasthenic syndrome is important because treatment with cholinesterase inhibitors can produce symptomatic improvement.

Differential immunohistological features of inflammatory myopathies and dysferlinopathy.

This study was performed in order to characterize the types of the infiltrating cells, and the expression profiles of major histocompatibility complex (MHC) class I and membrane attack complex (MAC) in patients with inflammatory myopathies and dysferlinopathy. Immunohistochemical stains were performed using monoclonal antibodies against several inflammatory cell types, MHC class I, and MAC in muscles from inflammatory myopathies and dysferlinopathy. There was significant difference in the types of infiltrating cells between polymyositis (PM), dermatomyositis (DM), and dysferlinopathy, including significantly high CD4+/CD8+ T cell ratio and B/T cell ratio in DM. In dysferlinopathy, CD4+ T cells were the most abundant and the proportions of infiltrating cell types were similar to those of DM. MHC class I was expressed in muscle fibers of PM and DM regardless of the presence of inflammatory infiltrates. MAC was expressed in necrotic fibers and vessels of PM and DM. One patient with early stage DM had a MAC deposits on endomysial capillaries. In dysferlinopathy, MAC deposit was also observed on the sarcolemma of nonnecrotic fibers. The analysis of inflammatory cells, MHC class I expressions and MAC deposits may help to differentiate dysferlinopathy from idiopathic inflammatory myopathy.

Novel CLCN1 mutations and clinical features of Korean patients with myotonia congenita.

Myotonia congenita (MC) is a form of nondystrophic myotonia caused by a mutation of CLCN1, which encodes human skeletal muscle chloride channel (CLC-1). We performed sequence analysis of all coding regions of CLCN1 in patients clinically diagnosed with MC, and identified 10 unrelated Korean patients harboring mutations. Detailed clinical analysis was performed in these patients to identify their clinical characteristics in relation to their genotypes. The CLCN1 mutational analyses revealed nine different point mutations. Of these, six (p.M128I, p.S189C, p.M373L, p.P480S, p.G523D, and p.M609K) were novel and could be unique among Koreans. While some features including predominant lower extremity involvement and normal to slightly elevated creatine kinase levels were consistently observed, general clinical features were highly variable in terms of age of onset, clinical severity, aggravating factors, and response to treatment. Our study is the first systematic study of MC in Korea, and shows its expanding clinical and genetic spectrums.

Clinical Diversity of SCN4A-Mutation-Associated Skeletal Muscle Sodium Channelopathy.

BACKGROUND AND PURPOSE: Mutations of the skeletal muscle sodium channel gene SCN4A, which is located on chromosome 17q23-25, are associated with various neuromuscular disorders that are labeled collectively as skeletal muscle sodium channelopathy. These disorders include hyperkalemic periodic paralysis (HYPP), hypokalemic periodic paralysis, paramyotonia congenita (PMC), potassium-aggravated myotonia, and congenital myasthenic syndrome. This study analyzed the clinical and mutational spectra of skeletal muscle sodium channelopathy in Korean subjects. METHODS: Six unrelated Korean patients with periodic paralysis or nondystrophic myotonia associated with SCN4A mutations were included in the study. For the mutational analysis of SCN4A, we performed a full sequence analysis of the gene using the patients' DNA. We also analyzed the patients' clinical history, physical findings, laboratory tests, and responses to treatment. RESULTS: We identified four different mutations (one of which was novel) in all of the patients examined. The novel heterozygous missense mutation, p.R225W, was found in one patient with mild nonpainful myotonia. Our patients exhibited various clinical phenotypes: pure myotonia in four, and PMC in one, and HYPP in one. The four patients with pure myotonia were initially diagnosed as having myotonia congenita (MC), but a previous analysis revealed no CLCN1 mutation. CONCLUSIONS: Clinical differentiating between sodium-channel myotonia (SCM) and MC is not easy, and it is suggested that a mutational analysis of both SCN4A and CLCN1 is essential for the differential diagnosis of SCM and MC.