• Journal of Genetic Medicine
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• v.20 no.2
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• pp.31-38
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• 2023

Rare diseases, even though defined as fewer than 20,000 in South Korea, with over 8,000 rare Mendelian disorders having been identified, they collectively impact 6-8% of the global population. Many of the rare diseases pose significant challenges to patients, patients' families, and the healthcare system. The diagnostic journey for rare disease patients is often lengthy and arduous, hampered by the genetic diversity and phenotypic complexity of these conditions. With the advent of next-generation sequencing technology and clinical implementation of exome sequencing (ES) and genome sequencing (GS), the diagnostic rate for rare diseases is 25-50% depending on the disease category. It is also allowing more rapid new gene-disease association discovery and equipping us to practice precision medicine by offering tailored medical management plans, early intervention, family planning options. However, a substantial number of patients remain undiagnosed, and it could be due to several factors. Some may not have genetic disorders. Some may have disease-causing variants that are not detectable or interpretable by ES and GS. It's also possible that some patient might have a disease-causing variant in a gene that hasn't yet been linked to a disease. For patients who remain undiagnosed, reanalysis of existing data has shown promises in providing new molecular diagnoses achieved by new gene-disease associations, new variant discovery, and variant reclassification, leading to a 5-10% increase in the diagnostic rate. More advanced approach such as long-read sequencing, transcriptome sequencing and integration of multi-omics data may provide potential values in uncovering elusive genetic causes.

• Molecules and Cells
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• v.27 no.1
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• pp.127-127
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• 2009

• Molecules and Cells
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• v.26 no.2
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• pp.175-180
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• 2008

$I{\kappa}B$ kinase (IKK), the pivotal kinase in signal-dependent activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), is composed of multiple protein components, including IKK ${\alpha}/{\beta}/{\gamma}$ core subunits. To investigate the regulation of the IKK complex, we immunoaffinity purified the IKK complex, and by MALDI-TOF mass spectrometry identified a splice variant of zinc finger protein 268 (ZNF268) as a novel IKKinteracting protein. Both the full-length and the spliced form of the ZNF268 protein were detected in a variety of mammalian tissues and cell lines. The genes were cloned and expressed by in vitro transcription/translation. Several deletion derivatives, such as KRAB domain (KRAB) on its own, the KRAB/spacer/4-zinc fingers (zF4), and the spacer/4-zinc fingers (zS4), were ectopically expressed in mammalian cells and exhibited had different subcellular locations. The KRAB-containing mutants were restricted to the nucleus, while zS4 was localized in the cytosol. TNF-${\alpha}$-induced NF-${\kappa}B$ activation was examined using these mutants and only zS4 was found to stimulate activation. Collectively, the results indicate that a spliced form of ZNF268 lacking the KRAB domain is located in the cytosol, where it seems to play a role in TNF-${\alpha}$-induced NF-${\kappa}B$ activation by interacting with the IKK complex.

• Genomics & Informatics
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• v.13 no.2
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• pp.31-39
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• 2015

Sequencing depth, which is directly related to the cost and time required for the generation, processing, and maintenance of next-generation sequencing data, is an important factor in the practical utilization of such data in clinical fields. Unfortunately, identifying an exome sequencing depth adequate for clinical use is a challenge that has not been addressed extensively. Here, we investigate the effect of exome sequencing depth on the discovery of sequence variants for clinical use. Toward this, we sequenced ten germ-line blood samples from breast cancer patients on the Illumina platform GAII(x) at a high depth of ${\sim}200{\times}$. We observed that most function-related diverse variants in the human exonic regions could be detected at a sequencing depth of $120{\times}$. Furthermore, investigation using a diagnostic gene set showed that the number of clinical variants identified using exome sequencing reached a plateau at an average sequencing depth of about $120{\times}$. Moreover, the phenomena were consistent across the breast cancer samples.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.14 no.1_2
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• pp.160-168
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• 1992

Ameloblastoma is an aggressive but benign epithelial neoplasm of odontogenic origin, and the occurrence of odontogenic epithelium in the wall of a dentigerous cyst is well-known entity. The presence of ameloblastic proliferation in the walls of odontogenic cysts has been reported for many years. Cahn in 1933 described a case in which he considered an ameloblastoma to have originated in a dentigerous cyst, and numerous other cases of ameloblastomatous proliferation have since been reported. In 1977, Robinson and Martinez described a distinct variant of ameloblastoma in which the response to curettage was found to be favorable with a recurrence rate of 25%. The gross and microscopic features indicated that this variant vas associated with a large cystic cavity with either luminal or mural proliferation of ameloblastic tumor cells, and they referred to this variant as unicystic ameloblastoma. Unicystic ameloblastoma occurs most commonly in the second and third decades of life, which is considerably younger than the average age of discovery for the classical ameloblastoma. For the accurate histopathological diagnosis of the unicystic ameloblastoma, the specimen obtained the excisional biopsy, complete enucleation or incisional biopsy from the multiple site of the lesion. This article provides histopathologic evidence of multilocular unicystic ameloblastoma in which ameloblastic tissue was associated with a dentigerous cyst that was found in a 31-year-old female, and complete radiographic, photographic, and microscopic documentation is presented.

• Korean Journal of Biological Psychiatry
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• v.2 no.1
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• pp.140-143
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• 1995

Tardive dyskinesia(TD), typically appearing as an undesirable side effect of a long term antipsychotic drug treatment has gained increased attention in recent times due to the discovery of many TD variants. This is a single case study of a patient who has undergone more than 8 years of high dosage antipsychotic treatment. After altering the type and dosage of antipsychotic medication 3 months prior to visit, the patient showed relatively abrupt onset symptoms of severe tremor and dystonia. These symptoms, appearing in clear consciousess, got better to a certain degree after 48 hours, worsened for 12 hours, and then improved again. Subsequently there was no continuing movement disorder. Several tests and consultation were carried out. However except for the medication factor, no other possible causes for such disabling symptoms were found. This clinical condition was thought to be akin to tardive tremor, a variant of TD. Furthermore, the course was atypical.

• 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.

• Genomics & Informatics
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• v.11 no.4
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• pp.191-199
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• 2013

High-throughput next-generation sequencing (NGS) technology produces a tremendous amount of raw sequence data. The challenges for researchers are to process the raw data, to map the sequences to genome, to discover variants that are different from the reference genome, and to prioritize/rank the variants for the question of interest. The recent development of many computational algorithms and programs has vastly improved the ability to translate sequence data into valuable information for disease gene identification. However, the NGS data analysis is complex and could be overwhelming for researchers who are not familiar with the process. Here, we outline the analysis pipeline and describe some of the most commonly used principles and tools for analyzing NGS data for disease gene identification.

• Korean Journal of Psychosomatic Medicine
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• v.25 no.1
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• pp.3-11
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• 2017

Objectives : The aim of this study was to draw attention toward so called 'behavioral variant frontotemporal dementia(bvFTD) phenocopy syndrome', which is difficult to discriminate with the primary psychiatric disorders, showing poor response to conventional therapeutic drugs, leading to higher risk to misdiagnoses and legal problems. Furthermore, the author insisted that our interest and study on them must be continued. Methods : English articles published during 2000 thru 2016 had been searched by internet with the combination of words such as 'frontotemporal', 'phenocopy' and 'behavioral', and reviewed. Besides, two clinical vignettes were described. Results : Precise diagnosis is important because patients' behavioral symptoms can influence on their families and community. However, disease-modifying treatment for bvFTD are not developed until now, and recent therapeutic drugs are only good for specific symptoms, while deterioration progresses in spite of proper psychiatric management. The possible bvFTD patients are not progressed into probable bvFTD clinically, showing no decline of cogntive and social function, no decrease of activity function, longer survival time, and normal neuroimaging for several years. Conclusions : Rather than expected, there are much more patients having clinical symptoms, course and diagnostic findings including neuroimaging, which are atypical to classical frontotemporal dementia and primary psychiatric disorders. If our knowledge and discriminating ability is improved, discovery rate of that cases will be increased. However, the identity of these atypical features are not clarified until now, it must be further actively investigated.

• Molecules and Cells
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• v.42 no.11
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• pp.783-793
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• 2019

When endoplasmic reticulum (ER) functions are perturbed, the ER induces several signaling pathways called unfolded protein response to reestablish ER homeostasis through three ER transmembrane proteins: inositol-requiring enzyme 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Although it is important to measure the activity of ATF6 that can indicate the status of the ER, no specific cell-based reporter assay is currently available. Here, we report a new cell-based method for monitoring ER stress based on the cleavage of $ATF6{\alpha}$ by sequential actions of proteases at the Golgi apparatus during ER stress. A new expressing vector was constructed by using fusion gene of GAL4 DNA binding domain (GAL4DBD) and activation domain derived from herpes simplex virus VP16 protein (VP16AD) followed by a human $ATF6{\alpha}$ N-terminal deletion variant. During ER stress, the GAL4DBD-VP16AD(GV)-$hATF6{\alpha}$ deletion variant was cleaved to liberate active transcription activator encompassing GV-$hATF6{\alpha}$ fragment which could translocate into the nucleus. The translocated GV-$hATF6{\alpha}$ fragment strongly induced the expression of firefly luciferase in HeLa Luciferase Reporter cell line containing a stably integrated 5X GAL4 site-luciferase gene. The established double stable reporter cell line HLR-GV-$hATF6{\alpha}$(333) represents an innovative tool to investigate regulated intramembrane proteolysis of $ATF6{\alpha}$. It can substitute active pATF6(N) binding motif-based reporter cell lines.