• The Korean Journal of Physiology and Pharmacology
• /
• 제28권4호
• /
• pp.313-322
• /
• 2024

Mutations within the SCN5A gene, which encodes the α-subunit 5 (Na_V1.5) of the voltage-gated Na⁺ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the Na_V1.5 current (I_Na) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of I_Na was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the co-expression of SCN1B with p.A385T/R504T revealed significant reduction of I_Na and slower recovery from inactivation, consistent with the loss-of-function in Na⁺ channels. The SCN1B dependent reduction of I_Na was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of Na_V1.5, respectively.

• Parasites, Hosts and Diseases
• /
• 제58권6호
• /
• pp.709-714
• /
• 2020

Knockdown resistance (kdr) mutations in the voltage-gated sodium channel (VGSC) of mosquitoes confer resistance to insecticides. Although insecticide resistance has been suspected to be widespread in the natural population of Aedes aegypti in Myanmar, only limited information is currently available. The overall prevalence and distribution of kdr mutations was analyzed in Ae. aegypti from Mandalay areas, Myanmar. Sequence analysis of the VGSC in Ae. aegypti from Myanmar revealed amino acid mutations at 13 and 11 positions in domains II and III of VGSC, respectively. High frequencies of S989P (68.6%), V1016G (73.5%), and F1534C (40.1%) were found in domains II and III. T1520I was also found, but the frequency was low (8.1%). The frequency of S989P/V1016G was high (55.0%), and the frequencies of V1016G/F1534C and S989P/V1016G/F1534C were also high at 30.1% and 23.5%, respectively. Novel mutations in domain II (L963Q, M976I, V977A, M994T, L995F, V996M/A, D998N, V999A, N1013D, and F1020S) and domain III (K1514R, Y1523H, V1529A, F1534L, F1537S, V1546A, F1551S, G1581D, and K1584R) were also identified. These results collectively suggest that high frequencies of kdr mutations were identified in Myanmar Ae. aegypti, indicating a high level of insecticide resistance.

• 한국광과학회:학술대회논문집
• /
• 한국광과학회 1997년도 학술대회지
• /
• pp.37-37
• /
• 1997

• Journal of Korean Neurosurgical Society
• /
• 제67권3호
• /
• pp.326-332
• /
• 2024

Intracranial vascular malformations typically encountered by pediatric neurosurgeons include arteriovenous malformations, vein of Galen malformations and cavernous malformations. While these remain amongst some of the most challenging lesions faced by patients and caregivers, the past decade has produced marked advances in the understanding of the pathophysiology of these conditions, with concomitant innovations in treatment. This article will highlight present and future perspectives relevant to these diseases, with a focus on an emerging approach utilizing disease-specific mutations to develop a novel taxonomy for these conditions.

• 한국환경성돌연변이발암원학회지
• /
• 제10권2호
• /
• pp.93-106
• /
• 1990

The Drosophila temperature-sensitive mutant shibire (shi) is paralyzed at restrictive temperature by a reversible block in synaptic transmission. To explore the functional relationship among shi gene products, viability and temperature-sensitive paralytic behavior were quantitaively analyzed for four shi alleles, shi$^{ts1}$, shi$^{ts2}$, shi$^{ts4}$, and shi$^{ST139}$, and their heteroallelic combinations. The hemizygous combination of shi alleles over deficiency was not completely lethal. shi$^{ts2}$ exhibited distinctively higher viability than other alleles. A novel behavior, bang sensitivity, was also found in shi/Df(1). This bang-sensitive paralytic behavior was compared with that of the typical bang-sensitive mutant flies. Heterozygotes, shi/+, are more severe in temperature sensitivity than deficiency hemizygotes, Df(1)/+. Heteroallelic combinations of shi were less sensitive to high temperature than homozygotes. Among all allelic combinations, shi$^{ts2}$/shi$^{ts4}$ showed an unexpected extreme reduction in temperature sensitivity. The results of allelic interactions among 4 shi alleles suggest that the shi mutations examined behave as antimorphic alleles and that the gene product of shi are likely to function in multimeric forms.

• Journal of Korean Neurosurgical Society
• /
• 제61권3호
• /
• pp.343-351
• /
• 2018

Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained. It is hoped that more representative in vitro and preclinical models-using both xenografted material and genetically engineered mice-will enable the development of novel chemotherapeutic agents and strategies for targeted drug delivery. This review provides a clinical overview of DIPG, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery.

• Journal of Genetic Medicine
• /
• 제10권2호
• /
• pp.109-112
• /
• 2013

Treacher Collins syndrome (TCS) is the most common and well known mandibulofacial dysostosis with characteristic clinical features including downward slanting of palpebral fissures, coloboma of the lower eyelid, hypoplastic zygomatic arches, micrognathia, macrostomia, microtia, and other deformities of the ears. TCS is caused by mutations in at least 3 genes involved in pre-rRNA transcription: TCOF1, POLR1D and POLR1C. We experienced a 1-day-old female infant with characteristic clinical features of TCS. A novel, heterozygotic mutation within the TCOF1 gene (c.3874_3875insG, p.Ala1292Glyfs*30) was identified to cause a premature stop codon.

• Clinical and Experimental Pediatrics
• /
• 제53권12호
• /
• pp.1018-1021
• /
• 2010

Townes-Brocks syndrome (TBS) is a rare autosomal dominant congenital disorder caused by mutations in the $SALL1$ gene. Its signs and symptoms overlap with other genetic syndromes, including VACTERL association, Pendred syndrome, Baller-Gerold syndrome, and cat eye syndrome. Structural vertebral abnormalities, hypoplasia of the thumb, and radial bone abnormalities, which are not usually associated with TBS, help in the differential diagnosis of these syndromes. We report the case of a family whose members were diagnosed with TBS with congenital hypothyroidism and had a novel $SALL1$ gene mutation.

• 고신대학교 의과대학 학술지
• /
• 제33권3호
• /
• pp.446-453
• /
• 2018

Pheochromocytomas might be sporadic or genetic. Genetic pheochromocytoma is associated with multiple endocrine neoplasia (MEN) type 2A, MEN type 2B, and von Hippel-Lindau (VHL) disease. RET mutations are identified in more than 90% of index cases of MEN2 and familial medullary thyroid cancer and in about 4-12% of apparent sporadic cases. Here, we report a 54-year-old man presenting with pheochromocytoma and renal cell carcinoma, who was identified as having a novel missense RET mutation.

• Annals of Clinical Neurophysiology
• /
• 제23권1호
• /
• pp.61-64
• /
• 2021

Adrenoleukodystrophy (ALD) is the most common peroxisomal disorder caused by mutations in the gene, ABCD1, causing abnormal accumulation of very-long-chain fatty acids in the nervous system and adrenal glands. There are various clinical manifestations of ALD. Here we report a 47-year-old male with adrenomyeloneuropathy with cerebral involvement who exhibited progressive gait disturbance and cognitive impairment. A novel frameshift variant (c.95del [p.Val32Alafs^*36]) in exon 1 of ABCD1 was identified. This report provides additional information regarding the various clinical characteristics of ALD.