• Genomics & Informatics
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• v.10 no.4
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• pp.214-219
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• 2012

The recent advent of next-generation sequencing technologies has dramatically changed the nature of biomedical research. Human genetics is no exception－it has never been easier to interrogate human patient genomes at the nucleotide level to identify disease-associated variants. To further facilitate the efficiency of this approach, whole exome sequencing (WES) was first developed in 2009. Over the past three years, multiple groups have demonstrated the power of WES through robust disease-associated variant discoveries across a diverse spectrum of human diseases. Here, we review the application of WES to different types of inherited human diseases and discuss analytical challenges and possible solutions, with the aim of providing a practical guide for the effective use of this technology.

• Proceedings of the Zoological Society Korea Conference
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• 2001.10a
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• pp.107.2-108
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• 2001

No Abstract, See Full Text

• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.18-22
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• 2005

Pompe disease is a genetic disorder caused by a deficiency of acid ${\alpha}$-glucosidase (GAA). This enzyme defect results in lysosomal glycogen accumulation in multiple tissues and cell types, with cardiac, skeletal, and smooth muscle cells the most seriously affected. Infantile-onset Pompe disease is uniformly lethal. Affected infants present in the first few months of life with hypotonia, generalized muscle weakness, and a hypertrophic cardiomyopathy, followed by death from cardiorespiratory failure or respiratory infection, usually by 1 year of age. Late-onset forms is characterized by a lack of severe cardiac involvement and a less severe short-term prognosis. Enzyme replacement therapy for Pompe disease is intended to address directly the underlying metabolic defect via intravenous infusions of recombinant human GAA to provide the missing enzyme. We experienced one case of Pompe disease in 3-years old boy that has improved his exercise ability and cardiac function after GAA enzyme replacement therapy.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.2
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• pp.1-7
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• 2023

Inherited metabolic disorders (IMD) are a group of disorders involving various metabolic pathways. Genetic diagnosis of IMD has been challenging because of extremely heterogeneous nature and extensive laboratory and/or phenotype overlap. Conventional genetic diagnosis was a gene-by-gene approach that needs a priori information on the causative genes that might underlie the IMD. Recent implementation of next-generation sequencing (NGS) technologies has changed the process of genetic diagnosis from a gene-by-gene approach to simultaneous analysis of targeted genes possibly associated with the IMD using gene panels or using whole exome/genome sequencing (WES/WGS) covering entire human genes. Clinical NGS tests can be a cost-effective approach for the rapid diagnosis of IMD with genetic heterogeneity and are becoming standard diagnostic procedures.

• Journal of Veterinary Clinics
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• v.21 no.2
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• pp.219-228
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• 2004

Heart diseases related to conduction system can be occurred by primary defects in conduction system and by secondary to morphological heart diseases or drug toxicities. Multiple molecular defects responsible for arrhythmogenesis, including mutations in ion channels, cytoplasmic ion-channel-interacting proteins, gap-junction proteins, transcription factors and a kinase subunit, were found to be associated with the aetiology of primary cardiac conduction defects, especially inherited form. Despite a big progress in unveiling human arrhythmogenesis, conduction defects in dog has not been well studied except sudden death syndrome in German shepherd. In this review, molecular genetics in cardiac arrhythmogenesis, inherited human diseases associated with conduction defects and similar diseases in dogs will be discussed.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.22 no.2
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• pp.53-57
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• 2022

Congenital metabolic disorders are rare inherited disorders resulting from a defect in biochemical and metabolic pathways affecting proteins, fats, carbohydrates metabolism or impaired organelle function. Depending on the abnormality of biochemical metabolism, various precursors and their abnormal metabolites can accumulate in the body and the final products which are critical in normal physiology can be deficient, resulting in disease. Congenital metabolic disorders present complicated medical conditions involving several human organ systems, including nervous system, eyes, liver, and kidneys. Various proteins and lipids are involved in the development and homeostasis of the skin, so many congenital metabolic disorders present abnormal changes in skin and hair. In this review, congenital metabolic diseases related to amino acid and lipid metabolism accompanying skin abnormalities will be discussed.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.9-17
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• 2005

Homocystinuria is a metabolic disorder caused by a deficiency of cystathionine ${\beta}$-synthase (CBS). Patients with homocystinuria show clinical symptoms such as mental retardation, lens dislocation, vascular disease with life-threatening thromboembolisms and skeletal deformities. Generally, the major treatments for CBS deficiency include pharmacologic doses of pyridoxine or dietary restriction of methionine. However, there is no effective treatment for this disease up till today and gene therapy can be an attractive novel approach to treatment of the disease. We investigated whether a recombinant adeno-associated virus could be used as a CBS gene transfer vector to reduce the excessive homocysteine level in the homocystinuria mouse model. Recombinant adeno-associated virus vector encoding the human CBS gene (rAAV-hCBS), driven by EF1-a promoter, was infused into CBS-deficient mice ($CBS^{-/-}$) via intramuscular (IM) and intraperitoneal (IP) injection. IP injection was more efficient than IM injection for prolongation of lives and reduction of plasma homocysteine levels. After 2 weeks of gene transfer by IP injection, serum homocysteine level was significantly decreased in treated mice compared with the age-matched controls and the life span was extended about 1.5 times. Also, increased expression of CBS gene was observed by immunohistochemical staining in livers of treated $CBS^{-/-}$ mice and microvesicular lipid droplets was decreased in cytoplasm of liver. These results demonstrate the possibility and efficacy of gene therapy by AAV gene transfer in homocystinuria mice.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.2
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• pp.59-64
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• 2015

Purpose: Lactate has two optical isomers, L-lactate and D-lactate. In human L-lactate is the most abundant enantiomer of lactate. As plasma and urinary levels of L-lactate is associated with inherited metabolic disorders in general, D-lactate have been linked to the presence of diabetes and inflammatory bowel disease. Previously developed techniques have shown several limitations to further evaluate D-lactate as a biomarker for this condition. In this paper, we describe a highly sensitive, specific and fast liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the analysis of D-, L-lactate in urine. Methods: D- and L-lactate were quantified using high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) with labelled internal standard. Samples were derivatized with (+)-O,O'-diacety-L-tartaric anhydride (DATAN) and seperated on a Poroshell 120 EC-C18 column. Results: Quantitative analysis of D-, and L-lactate was achieved successfully. Calibration curves were linear (r>0.999) over $0.5-100{\mu}g/mL$. Stabilities for samples were within the 10% varation. Inter- and Intra-day assay variations were below 10%. Conclusion: The presented method proved to be suitable for the quantitation of D- and L-lactate and opens the possibility to explore the use of D-lactate as a biomarker.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.42-48
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• 2012

Pompe disease is a rare lysosomal glycogen storage disorder caused by a total or partial deficiency of the acid ${\alpha}$-glucosidase (GAA) enzyme due to the GAA gene mutations. The classic infantile form of Pompe disease is a rapidly progressive multi-organ disease with hypotonia, generalized muscle weakness, and hypertrophic cardiomyopathy, usually leading to death in the first 2 years of life. Enzyme replacement therapy with recombinant human GAA has been shown to be effective and subsequently yielded promising results. Here, we present clinical and genetic characteristics of three Korean non-classic infantile Pompe patients, and the short term efficacy of enzyme replacement therapy. Considering that enzyme replacement therapy can change the natural course of infantile Pompe disease, early diagnosis and early initiation of treatment is critical to improving patient outcomes.

• YAKHAK HOEJI
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• v.60 no.1
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• pp.15-20
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• 2016

Globotriaosylsphingosine (lyso Gb3) is considered as one of the biomarkers for Fabry disease. A rapid and simple UPLC-MS/MS method was developed for the determination of reliable biomarker, lyso Gb3. Total analytical procedure takes only 15 min including sample preparation and MS/MS analysis. Limit of detection was 0.85 ng/ml (S/N=3). The calibration curve was linear over the range of 2.0~400.0 ng/ml ($R^2=0.9999$). Inter-day and intra-day assay accuracy were 93.4~100.6% (RSD, 0.6~6.0%) and 97.5~100.7% (RSD, 3.6~5.2%). Absolute recoveries of 97.6~98.6 showed excellence of a new analytical method. The method was applied to human and mice urines, proved the suitability for the quantification of lyso-Gb3 for screening, diagnosis and therapeutic monitoring of Fabry disease patients.