• Journal of Genetic Medicine
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• v.14 no.2
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• pp.56-61
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• 2017

Purpose: Neurofibromatosis type 2 (NF2) is characterized by multiple tumors, including vestibular schwannoma (VS) and others affecting cranial and peripheral nerves. NF2 is caused by mutation of the NF2 gene. The mutation spectrum of NF2 has not been characterized in Korean patients. In the current study, the clinical and genetic characteristics of Korean NF2 patients were analyzed. Materials and Methods: Twenty-five unrelated Korean families were enrolled according to the Manchester criteria. Genetic analysis was performed by direct sequencing and multiplex ligation-dependent probe amplification methods using genomic DNA from peripheral lymphocytes or tumor tissues. Results: All patients had bilateral/unilateral VS and/or other cranial and peripheral nerve tumors. Two patients were familial cases and the other 24 patients were sporadic. Germline NF2 mutations were detected in peripheral lymphocytes from both familial cases, but only in 26.1% of the 23 sporadic families. Somatic mutations were also found in tumor tissues from two of the sporadic families. These somatic mutations were not found in peripheral lymphocytes. A total of 10 different mutations including 2 novel mutations were found in 40.0% of studied families. Five mutations (50.0%) were located in exon 6 of NF2, the FERM domain coding region. Conclusion: Family history was an important factor in identifying germline NF2 mutations. Further study is required to investigate whether exon 6 is a mutation hotspot in Korean NF2 patients and its correlation to phenotypic severity.

• Childhood Kidney Diseases
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• v.8 no.1
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• pp.68-73
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• 2004

Both Gitelman syndrome and Bartter syndrome are autosomal recessively inherited renal tubular disorders characterized by hypokalemic metabolic alkalosis, salt wasting and normal to low blood pressure. Gitelman syndrome is caused by mutations in the thiazide-sensitive Na-Cl cotransporter (NCCT) and distinguished from Bartter syndrome, which is associated with mutations of several genes, by the presence of hypomagnesemia and hypocalciuria. In most of the patients with Gitelman syndrome, the disease manifests with transient episodes of muscular weakness and tetany in the adult period, but, often, is asymptomatic. We report here an 11 years-old female with Gitelman syndrome who presented with aggravation of epileptic seizure. The diagnostic work-up showed typical clinical features of metabolic alkalosis, hypokalemia, hypomagnesemia and hypocalciuria. We also identified a heterozygote mutation($^{642}$CGC(Arg)>TGC(Cys)) and an abnormal splicing in the SLC12A3 gene encoding NCCT.

• Molecules and Cells
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• v.40 no.7
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• pp.466-475
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• 2017

Dietary supplements have exhibited myriads of positive health effects on human health conditions and with the advent of new technological advances, including in the fields of proteomics, genomics, and metabolomics, biological and pharmacological activities of dietary supplements are being evaluated for their ameliorative effects in human ailments. Recent interests in understanding and discovering the molecular targets of phytochemical-gene-protein-metabolite dynamics resulted in discovery of a few protein signature candidates that could potentially be used to assess the effects of dietary supplements on human health. Persimmon (Diospyros kaki) is a folk medicine, commonly used as dietary supplement in China, Japan, and South Korea, owing to its different beneficial health effects including anti-diabetic implications. However, neither mechanism of action nor molecular biomarkers have been discovered that could either validate or be used to evaluate effects of persimmon on human health. In present study, Mass Spectrometry (MS)-based proteomic studies were accomplished to discover proteomic molecular signatures that could be used to understand therapeutic potentials of persimmon leaf extract (PLE) in diabetes amelioration. Saliva, serum, and urine samples were analyzed and we propose that salivary proteins can be used for evaluating treatment effectiveness and in improving patient compliance. The present discovery proteomics study demonstrates that salivary proteomic profile changes were found as a result of PLE treatment in prediabetic subjects that could specifically be used as potential protein signature candidates.

• Clinical and Experimental Emergency Medicine
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• v.3 no.3
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• pp.175-180
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• 2016

Objective Combination of ${\beta}_1-adrenergic$ receptor (AR) blockade and ${\beta}_2-AR$ activation might be a potential novel therapy for treating heart failure. However, use of ${\beta}-AR$ agonists and/or antagonists in the clinical setting is controversial because of the lack of information on cardiac inotropic or chronotropic regulation by AR signaling. Methods In this study, we performed hemodynamic evaluation by examining force frequency response (FFR), Frank-Starling relationship, and response to a non-selective ${\beta}-AR$ agonist (isoproterenol) in hearts isolated from 6-month-old transgenic (TG) mice overexpressing ${\beta}_1-$ and ${\beta}_2-ARs$ (${\beta}_1-$ and ${\beta}_2-AR$ TG mice, respectively). Results Cardiac physiologic consequences of ${\beta}_1-$ and ${\beta}_2-AR$ overexpression resulted in similar maximal response to isoproterenol and faster temporary decline of positive inotropic response in ${\beta}_2-AR$ TG mice. ${\beta}_1-AR$ TG mice showed a pronounced negative limb of FFR, whereas ${\beta}_2-AR$ TG mice showed high stimulation frequencies with low contractile depression during FFR. In contrast, Frank-Starling relationship was equally enhanced in both ${\beta}_1-$ and ${\beta}_2-AR$ TG mice. Conclusion Hemodynamic evaluation performed in the present showed a difference in ${\beta}_1-$ and ${\beta}_2-AR$ signaling, which may be due to the difference in the desensitization of ${\beta}_1-$ and ${\beta}_2-ARs$.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.4
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• pp.353-362
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• 2021

Cancer is a global health problem. There are diverse types of cancers, but there are several common pathways which lead to the development of cancer. Changes in gene expression might be the most common similarity found in almost all cancers. An understanding of the underlying changes in gene expression during cancer progression could lay a valuable foundation for the development of cancer therapeutics and even cancer vaccines. In this study, a well-known carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), was employed to induce changes in gene expression in normal stomach cells. MNNG is known to cause cancer by inducing damage to DNA in MNNG-treated mammalian cells and animals fed with this carcinogen. An analysis was performed by comparing the differentially expressed genes (DEGs) caused by MNNG treatment with DEGs in stomach cancer cell lines. To this end, methods of analysis for functional categorization and protein-protein interaction networks, such as gene ontology (GO), the database for annotation, visualization, and integrated discovery (DAVID), Kyoto encyclopedia of genes and genomics (KEGG) and search tool for the retrieval of interacting genes/proteins (STRING), were used. As a result of these analyses, MNNG-regulated specific genes and interaction networks of their protein products that contributed to stomach cancer were identified.

• Genomics & Informatics
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• v.20 no.2
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• pp.21.1-21.14
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• 2022

The influenza A viruses have high mutation rates and cause a serious health problem worldwide. Therefore, this study focused on genome characterization of the viruses isolated from Thai patients based on the next-generation sequencing technology. The nasal swabs were collected from patients with influenza-like illness in Thailand during 2017-2018. Then, the influenza A viruses were detected by reverse transcription-quantitative polymerase chain reaction and isolated by MDCK cells. The viral genomes were amplified and sequenced by Illumina MiSeq platform. Whole genome sequences were used for characterization, phylogenetic construction, mutation analysis and nucleotide diversity of the viruses. The result revealed that 90 samples were positive for the viruses including 44 of A/H1N1 and 46 of A/H3N2. Among these, 43 samples were successfully isolated and then the viral genomes of 25 samples were completely amplified. Finally, 17 whole genomes of the viruses (A/H1N1, n=12 and A/H3N2, n=5) were successfully sequenced with an average of 232,578 mapped reads and 1,720 genome coverage per sample. Phylogenetic analysis demonstrated that the A/H1N1 viruses were distinguishable from the recommended vaccine strains. However, the A/H3N2 viruses from this study were closely related to the recommended vaccine strains. The nonsynonymous mutations were found in all genes of both viruses, especially in hemagglutinin (HA) and neuraminidase (NA) genes. The nucleotide diversity analysis revealed negative selection in the PB1, PA, HA, and NA genes of the A/H1N1 viruses. High-throughput data in this study allow for genetic characterization of circulating influenza viruses which would be crucial for preparation against pandemic and epidemic outbreaks in the future.

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.72-79
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• 2007

Purpose : Glycogen storage disease type III (GSD-III) is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme, amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), is responsible for the debranching of the glycogen molecule during catabolism. The disease shows clinical and biochemical heterogeneity, reflecting genotype-phenotype heterogeneity among different patients. In this study, we aim at analyzing mutations of the AGL gene in three unrelated Korean GSD-III patients, and characterizing their clinical and laboratory findings. Methods : We characterized the clinical features of three unrelated Korean GSD-III patients by biochemical, histological and imaging studies. The 35 exons and part of exon-intron boundaries of AGL were analyzed by direct sequencing using genomic DNA extracted from the peripheral leukocytes of patients. Results : Diverse clinical features were observed in these patients including hepatomegaly (all patients), seizures (patient 2), grow th failure (patients 1 and 2), hyperlipidemia (patients 1 and 3), raised transaminase and creatine kinase concentrations (all patients), and mild cardiomyopathy (patient 2). Liver transplantation w as performed in patient 2 due to progressive hepatic fibrosis. A dministration of uncooked corn starch maintained normoglycemia and improved biochemical and growth profiles. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 had c.1510_1511insT (p.Y 504L fsX 10), and patient 3 had c.3416 T >C (p.L 1139P) and c.1735+1 G>T (p.Y 538_R578delfsX 4) mutations. A part from the p.R428K mutation, the 4 other substitutions identified w ere nov el. Conclusion : GSD-III patients display variable phenotypic characteristics resembling those of GSD-Ia. Molecular defects in the AGL gene of Korean GSD-III patients are genetically heterogeneous.

• Journal of Genetic Medicine
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• v.4 no.2
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• pp.133-141
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• 2007

Purpose : Cri-du-Chat syndrome (CdCs) is a rare but clinically recongnizable condition with an estimated incidence of 1:50,000 live births. The clinical characteristics of the syndrome include severe psychomotor and mental retardation, microcephaly, hypertelorism, hypotonia, and slow growth. Also the size of the chromosome 5p deletion ranges were known from the region 5p13 to the terminal region. In this study, we report the spectrum of 5p deletion in Korean 20 pts. with CdCs and genotype-phenotype associations in CdCs. Methods : In order to delineate genotype-phenotype correlation, molecular cytogenetic studies including GTG banding and clinical characterization were performed on Korean 20 pts with CdCs including parents. CGH array and Fluorescence in situ hybridization (FISH) analysis were used to confirm a terminal deletion karyotype and map more precisely the location of the deletion breakpoint. Results : Molecular analysis of the spectrum of 5p deletion revealed 9 pts (45%) with a del (5)(p14), 7 pts. (35%) a del (5)(p13), 3 pts. (15%) a del (5)(p15.1) and 1 pt. (5%) a del (5)(p15.2) in 20 pts with CdCs. 4(20%)pts were identified to have additional chromosome abnormalites of deficiency and duplication involving chromosomes of 6, 8, 18, & 22. Parental study identified 3 familial case (2 paternal and 1 maternal origin) showing parents being a balanced translocation carrier. And the comparison study of the deletion break points among these 20 pts. with their phenotype has showed the varying clinical pheno-types in the CdCs critical region. Conclusion : The characterization of 5p deletion including parental study may help to delineate the genotypephenotype correlation in CdCs. Also these molecular cytogenetic analyses will be able to offer better information for accurate genetic diagnosis in CdCs and further make possible useful genetic counseling in pts. and family.

• Clinical and Experimental Reproductive Medicine
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• v.44 no.4
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• pp.207-213
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• 2017

Objective: This study investigated the prevalence of infections with human papillomavirus, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, and Mycoplasma genitalium in the semen of Korean infertile couples and their associations with sperm quality. Methods: Semen specimens were collected from 400 men who underwent a fertility evaluation. Infection with above five pathogens was assessed in each specimen. Sperm quality was compared in the pathogen-infected group and the non-infected group. Results: The infection rates of human papillomavirus, C. trachomatis, U. urealyticum, M. hominis, and M. genitalium in the study subjects were 1.57%, 0.79%, 16.80%, 4.46%, and 1.31%, respectively. The rate of morphological normality in the U. urealyticum-infected group was significantly lower than in those not infected with U. urealyticum. In a subgroup analysis of normozoospermic samples, the semen volume and the total sperm count in the pathogen-infected group were significantly lower than in the non-infected group. Conclusion: Our results suggest that infection with U. urealyticum alone and any of the five sexually transmitted infections are likely to affect sperm morphology and semen volume, respectively.

• Journal of Genetic Medicine
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• v.2 no.1
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• pp.11-15
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• 1998

This paper reports 3 cases with 46,XX sex reversed male. Three 46,XX hypogonadal subjects showed complete sex reversal and had normal phallus and azoospermia. We studied them under clinical, cytogenetic and molecular aspects to find out the origin of the sex reversal. Patients had markedly elevated serum follicle-stimulating hormone (FSH) and lutenizing hormone (LH) and decreased or normal range of serum testosterone. The testicular volumes were small (3-8ml). Testicular biopsy showed Leydig cell hyperplasia and atrophy of seminiferous tubules. We obtained the results of normal 46,XX, and the presence of Y chromosome mosaicism was ruled out through XY dual fluorescent in situ hybridization (FISH). By using polymerase chain reaction (PCR), we amplified short arm (SRY, PABY, ZFY and DYS14), centromere (DYZ3), and heterochromatin (DYZ1) region of the Y chromosome. PCR amplification of DNA from these patients showed the presence of the sex-determining region of the Y chromosome (SRY) but didn't show the centromere and heterochromatin region sequence. The SRY gene was detected in all the three patients. Amplification patterns of the other regions were different in these patients; one had four amplified loci (PABY+, SRY+, ZFY+, DYS14+), another had two loci (SRY+, ZFY+) and the other had two loci (PABY+, SRY+). We have found that each patient's translocation elements had different breakpoints at upstream and downstream of the SRY gene region. We conclude that the testicular development in 46,XX male patients were due to insertion or translocation of SRY gene into X chromosome or autosomes.