• Journal of Genetic Medicine
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• 제20권2호
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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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• 제27권1호
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• pp.127-127
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• 2009

• Molecules and Cells
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• 제26권2호
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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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• 제13권2호
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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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• 제14권1_2호
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• pp.160-168
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• 1992

저자는 31세 여자환자의 좌측하악부에서 매복된 제3대구치 주위의 함치성 낭종에서 기원한 Group 3a type의 다방성의 낭종성 법랑아세포종을 경험하여 병소에 포함된 치아 발거슬 및 enucleation/curettage로 현재까지 재발없이 치유되었기에 병리조직학적 소견을 중심으로 문헌고찰과 함께 보고하는 바이다.

• 생물정신의학
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• 제2권1호
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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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• 제10권4호
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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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• 제11권4호
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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.

• 정신신체의학
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• 제25권1호
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• pp.3-11
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• 2017

연구목적 소위 '행동증상 아형 전두측두엽 치매 표현형모사 증후군(behavioral variant frontotemporal dementia phenocopy syndrome)' 환자들은 일차성 정신장애와 감별이 힘들고, 기존의 치료 약물에 대한 반응도 회의적이어서, 오진의 위험과 법적 문제의 유발 가능성이 높으므로, 이러한 양상을 보이는 환자군에 대한 지속적인 관심과 연구가 필요함을 환기 시키기 위해서 본 연구를 시행하였다. 방법 2000년 부터 2016년 까지 발행된 영문 학술지에 게재된 논문을 인터넷에서 'frontotemporal', 'phenocopy', 'behavioral'과 같은 단어의 조합으로 검색하여 찾은 참고문헌을 정리, 고찰하였다. 또한 저자가 직접 경험한 두 증례를 간략히 기술하였다. 결과 환자의 행동 증상은 가족과 지역사회에 큰 영향을 끼치므로 행동증상 아형 전두측두엽 치매에서 정확한 진단이 중요하다. 그러나, 행동증상 아형 전두측두엽 치매에서 현재까지 질병 수정 치료법은 개발되지 않았으며, 현재의 약물학적 치료는 특수한 증상에 도움이 될 뿐이고, 적절한 정신의학적 치료에도 불구하고 점진적인 퇴행이 진행된다. 상당수의 '행동증상 아형 전두측두엽 치매 의심(possible bvFTD)' 환자에서 임상적으로 '행동증상 아형 전두측두엽 치매 가능(probable bvFTD)'으로 진행되지 않으며, 인지기능이나 사회적 기능이 저하되지 않고, 활동 기능의 저하를 보이지 않으며, 생존기간이 조금 더 길고, 수년에 걸쳐서 정상적인 뇌영상화 검사 소견을 보인다. 결론 환전두측두엽 치매 및 일차성 정신장애 환자에서 보이는 전형적인 임상적 양상이나 경과, 뇌영상화 검사를 포함한 진단적 평가와는 다른 비전형적인 소견을 보이는 환자군들은 생각보다 많으며, 정신의학과 의사들이 이에 대한 의학적 지식과 판별 능력이 발전되면, 그 발견의 비율은 훨씬 더 높아질 것이다. 그러나, 현재로서는 이러한 비전형적인 환자군의 정체에 대해서는 이견이 많으며, 향후 적극적인 연구가 행해져야할 분야이다.

• Molecules and Cells
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• 제42권11호
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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.