• Journal of The Korean Society of Inherited Metabolic disease
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• 제13권2호
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• pp.104-110
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• 2013

Purpose: Phenylketonuria (PKU) is the first inherited metabolic disease of which treatment is known. We performed this study to find out clinical symptoms and prognosis of tetrahydrobiopterin (BH4) responsive PKU patients and genetic relation. Methods: Clinical, biochemical, genetic analysis were done retrospectively in 23 patients diagnosed BH4 responsive PKU in Soonchunhyang University Hospital from March 2000 to September 2012. Results: Patients were classified to mild hyperphenylalaninemia and mild phenylketonuria with initial plasma phenylalanine level below 20 mg/dL. After BH4 loading, blood phenylalanine decrease level ranged between 37% and 99%. Initial treatment with low phenylalanine formula or BH4 was started before 2 month after birth except 2 patients. And one of them resulted in developmental delay in language and social activity. The others showed satisfactory progress without developmental delay. In genetic analysis, of 46 allele, R241C allele mutation was identified most commonly (41%). R241C/A259T, R241C/R243Q, R241C/V388M, R241C/T278I was detected in 5 (21.7%), 3 (13%), 2 (8%), 2 (8%) patients, respectively. Conclusion: R241C mutation was detected most frequently in this study group and R243Q mutation which is known to be prevalent in Korean PKU patients was found in 4 patients (8.6%). Early diagnosis and treatment is important in PKU patients.

• Development and Reproduction
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• 제23권3호
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• pp.213-221
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• 2019

The epididymal fat of mouse is a part of visceral fat deposit and is divided into the distal or proximal part based on its histochemical characteristics. Even though the formation of the epididymal fat pad begins before the birth, a detailed adipogenic procedure of the epididymal fat has not been revealed. The epididymal fat pad becomes enlarged and expended with age, and expressional changes of numerous genes are associated with the maturation of fat tissues. In the present research, expressional patterns of adipose tissue-related genes in the distal epididymal fat of mouse at 2, 5, 8, and 12 months of postnatal age were determined by a quantitative real-time polymerase chain reaction (PCR) analysis. The lowest transcript levels of fatty acid binding protein 4 (Fabp4), lipoprotein lipase (Lpl), delta like non-canonical Notch ligand 1 (Dlk1), peroxisome proliferator-activated receptor gamma (Pparg), leptin (Lep), adiponectin (Adipoq), and resistin (Retn) were detected at 2 months of age, except fatty acid synthase (Fasn) showing the lowest level at 5 months of age. Even though expression of Lep and Fabp4 were gradually increased until 12 months of age, significant increases of Pparg and Adipoq transcript levels were continued until 8 months of age. The transcript levels of Lpl, Rent, Dlk1, and Fasn were significantly increased at 8 months of age, compared with those at 2 months of age. The current findings suggest that the expansion of the distal epididymal fat of mouse during postnatal period would be companied with differential expression of various adipocyte-associated molecules.

• Clinical and Experimental Pediatrics
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• 제62권2호
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• pp.55-61
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• 2019

Purpose: Myotonic dystrophy, also known as dystrophia myotonica (DM), is an autosomal dominant disorder with 2 genetically distinct forms. DM type 1 (DM1) is the more common form and is caused by abnormal expansion of cytosine/thymine/guanine (CTG) repeats in the DM protein kinase (DMPK ) gene. Our study aimed to determine whether the age of onset is correlated with CTG repeat length in a population of pediatric patients with DM1. Methods: We retrospectively identified 30 pediatric patients with DM1 that underwent DMPK testing, of which the clinical data of 17 was sufficient. The cohort was divided into 2 subgroups based on the clinical phenotype (congenital-onset vs. late-onset) and number of CTG repeats (<1,000 vs. ${\geq}1,000$). Results: We found no significant difference between the age of onset and CTG repeat length in our pediatric patient population. Based on clinical subgrouping, we found that the congenital-onset subgroup was statistically different with respect to several variables, including prematurity, rate of admission to neonatal intensive care unit, need for respiratory support at birth, hypotonia, dysphagia, ventilator dependence, and functional status on last visit, compared to the late-onset subgroup. Based on genetic subgrouping, we found a single variable (poor feeding in neonate) that was significantly different in the large CTG subgroup than that in the small CTG subgroup. Conclusion: Clinical variables exhibiting statistically significant differences between the subgroups should be focused on prognosis and designing tailored management approaches for the patients; our findings will contribute to achieve this important goal for treating patients with DM1.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.82-82
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• 2003

Offspring have been produced from somatic cells in a number of species. This biotechnology introduced a new phenomenon in reprogramming and differentiation of somatic cell, namely totipotency. However, birth of oversized calves and perinatal abnormalities such as increased gestation length, lack of spontaneous parturition, higher incidence of dystocia, and reduced perinatal viability of offspring are frequently observed in pregnancies of cloned bovine fetuses. Disturbance of feto-placenta has been proposed as likely causes for abnomal growth. However. Little is known the mechanism responsible for the perinatal problems. Therefore, we focused on gestation length in somatic cell nuclear recipient cows. To solve this issues, placental tissues of control and cloned bovine were obtained by a cesarean section (C-section) before 5 days of paturition. Total RNA from control and cloned bovine placenta was extractd by TRIzol reagent. GeneFishing DEG kits (Seegene) were used to identify differentially expression genes. Total RNA (3 ug) were synthesized by M-MLV reverse transcriptase (200 u/ul) with 10 uM dT-annealing control primer (ACP1) at 42C for 90 min. Then, first-strand cDNA (50 ng) was amplified using the 5 uM arbitary ACP (1-20) and 10 uM dT-ACP2 primers. Some specific expression genes were amplified, Now, we are cloning and sequencing. These finding strongly can be support to solve the problems for parturition delay in nuclear transfer cows, suggest that placenta specific proteins are key indicators for the aberration of gestation and placental function in cows.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• 제26권1호
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• pp.69-75
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• 2022

Backgrounds/Aims: Progressive familial intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease requiring liver transplantation (LT). The objective of this study was to investigate the clinicopathological features and posttransplant courses of seven LT recipients with PFIC. Methods: This was a retrospective single-center study of patients with PFIC who underwent LT from January 2013 to June 2020. Results: Two and five patients were diagnosed with PFIC type 1 and type 2, respectively. For all seven patients, age of PFIC onset was at birth. Jaundice was present in all cases. Mean pretransplant total and direct bilirubin levels were 16.1 ± 8.1 mg/dL and 12.4 ± 6.2 mg/dL, respectively. Median patient age and body weight at LT were 10 months and 7 kg, respectively. Types of donors were mothers of patients in four and deceased donors in three. All five patients with PFIC type 2 recovered uneventfully. One patient each with PFIC type 1 underwent retransplantation due to graft failure or died due to multi-organ failure. Overall graft and patient survival rates at five years were 66.7% and 83.3%, respectively. Bile salt export pump immunohistochemical staining showed normal canalicular expression in two patients with PFIC type 1, focal loss in two patients with PFIC type 2, and total loss in three patients with PFIC type 2. Conclusions: LT is currently the only effective treatment for PFIC-associated end-stage liver diseases. It is mandatory to perform regular follow-up due to the risk of complications including steatohepatitis, especially for patients with PFIC type 1.

• Journal of Genetic Medicine
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• 제10권1호
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• pp.38-42
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• 2013

Purpose: The purpose of this study was to assess the characteristics of achondroplasia (ACH) diagnosed in fetuses or neonates and to evaluate the usefulness of a molecular genetic testing to confirm ACH. Materials and Methods: The medical and ultrasonographic records of 16 pregnant women, who had molecular genetic testing for ACH performed on their fetus or neonate at the Cheil General Hospital between February 1999 and April 2013, were retrospectively analyzed. Detection of G1138A and G1138C mutations of the fibroblast growth factor receptor 3 (FGFR3) gene was accomplished by polymerase chain reaction - restriction fragment length polymorphism analysis. Results: Of the eight fetuses and two neonates who were suspected of having ACH during pregnancy, four fetuses and one neonate was confirmed to have ACH and they all carried the heterozygous G1138A mutation. Out of 6 cases which had a history of ACH in prior pregnancies, three had genetic information for the previous fetuses while the other three did not. All six fetuses had no mutations at G380R. However, the one fetus of pregnant woman with non-confirmed ACH showed shortened long bone on ultrasound thereafter and the fetus was identified as having oto-spondylo-megaepiphyseal dysplasia after birth. Conclusion: Korean patients with achondroplasia have the heterozygous G1138A mutation that is most commonly defined in other countries. Molecular genetic evaluations of ACH are helpful not only for establishing diagnosis but for appropriate counseling with subsequent pregnancies.

• Journal of The Korean Society of Inherited Metabolic disease
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• 제16권1호
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• pp.47-51
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• 2016

Propionic acidemia (PA) is an autosomal recessively inherited disorder of the organic acid metabolism. It is caused by a deficiency of propionyl-CoA carboxylase (PCC). PCC is a heteropolymeric enzyme composed of ${\alpha}$- and ${\beta}$-subunits. The clinical symptoms of PA are heterogeneous and present vomiting, dehydration, hypotonia, and lethargy, and it can result in death. The typical presentations of neonatal onset PA are life-threatening metabolic acidosis and hyperammonemia. Here, we described a case of neonatal onset PA with mild clinical presentations. She was born to a healthy mother without complications. No significant illness was observed until nine days after birth. She started exhibiting poor oral feeding, vomiting, lethargy, and hypotonia at ten days old. Her laboratory results showed mild hyperammonemia and acidosis. The initial diagnosis was neonatal sepsis and she was treated with antibiotics. However, her clinical symptoms didn't improve. So we considered a metabolic disease. She was given nothing by mouth and intravenous hydration and nutrition support was performed. Propionylglycine and 3-hydroxypropionic acid were showed high concentrations in urine by gas chromatograph mass spectrometry (GC-MS). C3 level of acylcarnitine analysis elevated 10.4 uM/L (range, 0.200-5.00) in plasma. We took gene analysis for PA to be based on the symptoms and laboratory results. We detected PCCB gene mutation and diagnosed PA. She survived without severe neurologic defects and complications and was hospitalized only three times with upper respiratory tract infections for 7 years. We report a case of a ten days old neonate with PA presenting without severe metabolic acidosis and hyperammonemia who was effectively treated with early aggressive care and conventional methods.

• Asian-Australasian Journal of Animal Sciences
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• 제27권12호
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• pp.1695-1704
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• 2014

Maternal malnutrition during pregnancy may give rise to female offspring with disrupted ovary functions in adult age. Neonatal ovary development predisposes adult ovary function, yet the effect of maternal nutrition on the neonatal ovary has not been described. Therefore, here we show the impact of maternal protein restriction on the expression of folliculogenic and steroidogenic genes, their regulatory microRNAs and promoter DNA methylation in the ovary of neonatal piglets. Sows were fed either standard-protein (SP, 15% crude protein) or low-protein (LP, 7.5% crude protein) diets throughout gestation. Female piglets born to LP sows showed significantly decreased ovary weight relative to body weight (p<0.05) at birth, which was accompanied with an increased serum estradiol level (p<0.05). The LP piglets demonstrated higher ratio of bcl-2 associated X protein/B cell lymphoma/leukemia-2 mRNA (p<0.01), which was associated with up-regulated mRNA expression of bone morphogenic protein 4 (BMP4) (p<0.05) and proliferating cell nuclear antigen (PCNA) (p<0.05). The steroidogenic gene, cytochrome P450 aromatase (CYP19A1) was significantly down-regulated (p<0.05) in LP piglets. The alterations in ovarian gene expression were associated with a significant down-regulation of follicle-stimulating hormone receptor mRNA expression (p<0.05) in LP piglets. Moreover, three microRNAs, including miR-423-5p targeting both CYP19A1 and PCNA, miR-378 targeting CYP19A1 and miR-210 targeting BMP4, were significantly down-regulated (p<0.05) in the ovary of LP piglets. These results suggest that microRNAs are involved in mediating the effect of maternal protein restriction on ovarian function through regulating the expression of folliculogenic and steroidogenic genes in newborn piglets.

• Journal of The Korean Society of Inherited Metabolic disease
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• 제15권3호
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• pp.101-109
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• 2015

Classic galactosemia (OMIM #230400) is an autosomal recessive inherited metaboic disorder caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT, EC2.7.7.12) due to mutations in the GALT gene. If untreated, classic galactosemia is a potentially lethal disease presenting with poor feeding, vomiting, jaundice, liver failure, increased bleeding tendency, and septicemia leading to death within a few days after birth. Since 2006, expansion of newborn screening has been enabled the early diagnosis and early intervention of classic galactosemia in Korea. However, newborn screening, followup testing for confirmatory diagnosis and intervention for galactosemia continue to present challenges. In Korea, the prevalence of the classic galactosemia is considered relatively low compared to that of western countries. And the genotype is also clearly different from those of other population. Therefore, our own guideline for confirmatory diagnosis and intervention is needed. Here, the diagnostic algorithm for galactosemia after positive newborn screening result in Korea has been proposed. Considering the low prevalence and different mutation spectrum in Koreans, the early mutation analysis of GALT gene could be a useful tool for the accurate diagnosis and making any treatment decision.

• Journal of The Korean Society of Inherited Metabolic disease
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• 제18권1호
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• pp.23-29
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• 2018

Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder characterized by hyperammonemia. CPS1D is caused by mutations in the CPS1 gene on chromosome 2q35. Based on the age of onset, there are two phenotypes: the neonatal type and the delayed-onset type. The severity of clinical manifestation depends on the degree of CPS1 residual enzymatic activity, and can result in hyperammonemia and neurological dysfunction. We report a case of CPS1D in a neonate who developed vomiting, decreased consciousness and hyperammonemia at 25th day after birth. She showed excellent response to treatment including hydration, ammonia-lowering drugs and a low-protein diet without hemodialysis. Her growth, development and neurological outcomes were fair at the last follow-up at 17 months of age.