• Clinical and Experimental Pediatrics
• /
• v.57 no.1
• /
• pp.50-53
• /
• 2014

Hemophagocytic lymphohistiocytosis (HLH) occurs in the primary form (genetic or familial) or secondary form (acquired). The familial form of HLH (FHL) is a potentially fatal autosomal recessive disorder that occurs because of constitutional defects in cell-mediated cytotoxicity. Here, we report a fatal neonatal case of type 2 FHL (FHL2) that involved a novel frameshift mutation. Clinically, the newborn presented with severe sepsis-like features and required mechanical ventilation and continuous venovenous hemodiafiltration. Flow cytometry analysis showed marked HLH and complete absence of intracytoplasmic perforin expression in cytotoxic cells; therefore, we performed molecular genetic analyses for PRF1 mutations, which showed that the patient had a compound heterozygous mutation in PRF1, that is, c.65delC ($p.Pro22Argfs^*2$) and c.1090_1091delCT ($p.Leu364Glufs^*93$). Clinical and genetic assessments for FHL are required for neonates with refractory fever and progressive multiple organ failure, particularly when there is no evidence of microbiological or metabolic cause.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.41 no.7
• /
• pp.907-913
• /
• 2012

Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene) is a polyphenol detected in grapes, rhubarb, and sugarcane. Although recent experimental data revealed that this compound is known to exhibit immunosuppressive and antitumorigenic activities in several cell lines, the molecular mechanisms underlying anticancer activity are poorly understood. In the present study, we investigated possible further mechanisms by which piceatannol exerts its anti-proliferative action in cultured human gastric cancer AGS cells. Piceatannol treatment resulted in the inhibition of growth and G1 arrest of the cell cycle in a concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by piceatannol was associated with the modulation of cyclin-dependent kinases (Cdks) and cyclins, up-regulation of the expression of Cdk inhibitor p21 (WAF1/CIP1) in both transcriptional and translational levels, and the inhibition of phosphorylation of retinoblastoma proteins and E2F1 expression. In addition, piceatannol treatment caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin $E_2$ synthesis.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.6 no.1
• /
• pp.15-23
• /
• 2006

Purpose: Glycogen storage disease type III (GSD-III), is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme is amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), which is responsible for the debranching of the glycogen molecule during catabolism. The disease has been demonstrated to show clinical and biochemical heterogeneity, reflecting the genotype-phenotype heterogeneity among different patients. In this study, we analyzed mutations of the AGL gene in three unrelated Korean GSD-III patients and discussed their clinical and laboratory implications. Methods: We studied three GSD-III patients and the clinical features were characterized. Sequence analysis of 35exons and part exon-intron boundaries of the AGLgene in patients were carried out by direct DNA sequencing method using genomic DNA isolated from patients' peripheral leukocytes. Results: The clinical features included hepatomegaly (in all patients), seizures (in patient 2), growth failure (in patients 1), hyperlipidemia (in patients 1 and 3), raised transaminases and creatinine kinase concentrations (in all patients) and mild EKG abnormalities (in patients 2). Liver transplantation was performed in patient 2due to progressive hepatic fibrosis. Administration of raw-corn-starch could maintain normoglycemia and improve the condition. 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 with c.1510_1511insT (p.Y504LfsX10), and patient 3 with c.3416 T>C (p.L1139P) and c.l735+1 G>T (Y538_R578delfsX4) mutations. Except R428K mutation, 4 other mutations identified in3 patients were novel. Conclusion: GSD-III patients have variable phenotypic characteristics resembling GSD-Ia. The molecular defects in the AGL gene of Korean GSD-III patients were genetically heterogeneous.

• Korean Journal of Clinical Laboratory Science
• /
• v.53 no.2
• /
• pp.151-157
• /
• 2021

Charcot-Marie-Tooth disease (CMT) is a slowly progressive hereditary degenerative disease and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated disorder characterized by weakness and sensory deficits. The purpose of this study was to analyze and compare the electrophysiological characteristics observed in sensory nerve conduction studies (SNCS) of both diseases. A retrospective study of 65 patients with a diagnosis of CIDP (N=35) and CMT type I (N=30) was performed. This study analyzed No potentials ratio, distal compound nerve action potential (dCNAP) of various nerve types, and a correlation coefficient analysis of the sensory nerve conduction velocity (SNCV). As a result, I found that CMT 1 was more severe systemic demyelinating and axonal polyneuropathy better than CIDP (P<0.05). In a quantitative analysis of dCNAP and SNCV, especially sural nerve was the most severe nerve injury observed in both diseases. In correlation and scatter plot analysis, CMT 1 showed relatively high correlations compared to CIDP based on the correlation coefficient analysis (Fisher's Z test) of SNCV. The results of this study suggested that CMT 1 showed the slowness in SNCV, one of the characteristics of demyelinating polyneuropathy, and this slowing had a uniform pattern. In conclusion, electrophysiological characteristic of SNCS may be useful in the diagnosis and research between patients with CMT 1 and CIDP.

• Journal of Life Science
• /
• v.31 no.10
• /
• pp.913-921
• /
• 2021

Limb-girdle muscular dystrophy (LGMD) which is characterized by progressive muscle weakening of the hip and shoulder shows both dominant and recessive inheritances with many pathogenic genes including TTN. This study performed to identify genetic causes of a male patient with late onset (45 years old) autosomal recessive LGMD and atrial flutter. By application of the whole exome sequencing, we identified bi-allelic variants of TTN gene in the patient. One allele had a single missense variant of [c.24124G>T (p.V8042F)], while the other allele consisted of three missense variants of [c.29222G>C (p.R9741P) + c.67490A>G (p.H22497R) + c.75376C>T (p.R25126C)]. The p.V8042F allele was transmitted from his mother, while the other haplotype allele was putatively transmitted from his father. His two unaffected sons had only the p.R9741P. These variants have been not reported or rarely reported in the public human genome databases (1,000 Genome, gnomAD, and KRGDB). Most variants were located in the highly conserved immunoglobulin or fibronectin domains and were predicted to be pathogenic by the in silico analyses. The TTN giant protein plays a key role in muscle assembly, force transmission at the Z-line, and maintenance of resting tension in the I-band. In conclusion, we think that these bi-allelic compound heterozygous mutations may play a role as the genetic causes of the LGMD phenotype.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.23 no.1
• /
• pp.25-30
• /
• 2023

Leigh syndrome is a rare progressive neurodegenerative mitochondrial disorder with clinical and genetic heterogeneity. Recently, balletic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes from Leigh and West syndrome to a rare syndrome CAGSSS characterized by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia syndrome (OMIM#616007). We describe a child with Korean Leigh syndrome with urologic manifestations resulting from a compound heterozygote mutation in IARS2. A 5-year-old girl visited the emergency room with a complaint of abdominal pain accompanied by abdominal distension. Abdominal-pelvic CT showed a markedly distended urinary bladder without definite obstructive lesions. She was diagnosed with neurogenic bladder dysfunction based on a urodynamic study. She had global delayed development due to neurologic regression after 6 months of age and a history of bilateral cataract surgery at the age of 2 years. Her brain magnetic resonance imaging showed symmetrically increased signal intensities in the bilateral putamen and caudate nuclei with diffuse cerebral atrophy. No gene variants were identified through whole-mitochondrial genome analysis. Whole exome sequencing was performed for diagnosis, and compound heterozygous pathogenic variants were identified in IARS2: c.2446C>T (p. Arg816Ter) and c.2450G>A (p. Arg817His). To the best of our knowledge, this is the first case report of bladder dysfunction manifestation in a patient with IARS2-related Leigh syndrome. Thus, it broadens the clinical and genetic spectrum of IARS2-associated diseases.

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