• Clinical and Experimental Pediatrics
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• v.61 no.12
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• pp.403-406
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• 2018

Floating-Harbor syndrome is a rare autosomal dominant genetic disorder associated with SRCAP mutation. To date, approximately 50 cases of Floating-Harbor syndrome have been reported, but none have been reported in Korea yet. Floating-Harbor syndrome is characterized by delayed bony maturation, unique facial features, and language impairment. Here, we present a 6-year-old boy with a triangular face, deep-set protruding eyes, low-set ears, wide nose with narrow nasal bridge, short philtrum, long thin lips, clinodactyly, and developmental delay that was transferred to our pediatric clinic for genetic evaluation. He showed progressive delay in the area of language and cognition-adaption as he grew. He had previously undergone chromosomal analysis at another hospital due to his language delay, but his karyotype was normal. We performed targeted exome sequencing, considering several syndromes with similar phenotypes. Library preparation was performed with the TruSight One sequencing panel, which enriches the sample for about 4,800 genes of clinical relevance. Massively parallel sequencing was conducted with NextSeq. An identified variant was confirmed by Sanger sequencing of the patient and his parents. Finally, the patient was confirmed as the first Korean case of Floating-Harbor syndrome with a novel SRCAP (Snf2 related CREBBP activator protein) mutation (c.7732dupT, p.Ser2578Phefs*6), resulting in early termination of the protein; it was not found in either of his healthy parents or a control population. To our knowledge, this is the first study to describe a boy with Floating-Harbor syndrome with a novel SRCAP mutation diagnosed by targeted exome sequencing in Korea.

• Genomics & Informatics
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• v.17 no.4
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• pp.42.1-42.6
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• 2019

Robust identification of genetic alterations is important for the diagnosis and subsequent treatment of tumors. Screening for genetic alterations using tumor tissue samples may lead to biased interpretations because of the heterogeneous nature of the tumor mass. Liquid biopsy has been suggested as an attractive tool for the non-invasive follow-up of cancer treatment outcomes. In this study, we aimed to verify whether the mutations identified in primary tumor tissue samples could be consistently detected in plasma cell-free DNA (cfDNA) by digital polymerase chain reaction (dPCR). We first examined the genetic alteration profiles of three colorectal cancer (CRC) tissue samples by targeted next-generation sequencing (NGS) and identified 11 non-silent amino acid changes across six cancer-related genes (APC, KRAS, TP53, TERT, ARIDIA, and BRCA1). All three samples had KRAS mutations (G12V, G12C, and G13D), which were well-known driver events. Therefore, we examined the KRAS mutations by dPCR. When we examined the three KRAS mutations by dPCR using tumor tissue samples, all of them were consistently detected and the variant allele frequencies (VAFs) of the mutations were almost identical between targeted NGS and dPCR. When we examined the KRAS mutations using the plasma cfDNA of the three CRC patients by dPCR, all three mutations were consistently identified. However, the VAFs were lower (range, 0.166% to 2.638%) than those obtained using the CRC tissue samples. In conclusion, we confirmed that the KRAS mutations identified from CRC tumor tissue samples were consistently detected in the plasma cfDNA of the three CRC patients by dPCR.

• Plant Biotechnology Reports
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• v.5 no.1
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• pp.9-17
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• 2011

With the development of next-generation sequencing technology, ever-expanding databases of genetic information from various organisms are available to researchers. However, our ability to study the biological meaning of genetic information and to apply our genetic knowledge to produce genetically modified crops and animals is limited, largely due to the lack of molecular tools to manipulate genomes. Recently, targeted cleavage of the genome using engineered DNA scissors called zinc finger nucleases (ZFNs) has successfully supported the precise manipulation of genetic information in various cells, animals, and plants. In this review, we will discuss the development and applications of ZFN technology for genome engineering and highlight recent reports on its use in plants.

• Journal of Genetic Medicine
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• v.19 no.2
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• pp.57-62
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• 2022

Systemic autoinflammatory diseases (SAIDs) are characterized by unprovoked inflammatory episodes such as recurrent/periodic fever, serositis, skin lesions, abdominal symptoms, arthritis/arthralgia, and central nervous system involvement. Genetic diagnosis of SAIDs has been challenging because disease manifestations overlap among themselves and with other immunological disease categories, such as infection and autoimmune diseases. However, the advent of next-generation sequencing (NGS) technologies and expanding knowledge about the innate immunity and inflammation have made the routine genetic diagnosis of SAIDs possible. Here, we review the recurrent/periodic fevers, other recently identified autoinflammatory diseases, and type I interferonopathies, and discuss the clinical usefulness of NGS targeted sequencing for SAIDs, and recent advance of understandings for this heterogeneous disease group as for underlying primary immunodeficiency.

• Journal of Genetic Medicine
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• v.7 no.2
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• pp.119-124
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• 2010

More than 7,000 rare Mendelian diseases have been reported, but less than half of all rare monogenic disorders has been discovered. In addition, the majority of mutations that are known to cause Mendelian disorders are located in protein-coding regions. Therefore, exome sequencing is an efficient strategy to selectively sequence the coding regions of the human genome to identify novel genes associated with rare genetic disorders. The "exome" represents all of the exons in the human genome, constituting about 1.5% of the human genome. Exome sequencing is carried out by targeted capture and intense parallel sequencing. After the first report of successful exome sequencing for the identification of causal genes and mutations in Freeman Sheldon syndrome, exome sequencing has become a standard approach to identify genes in rare Mendelian disorders. Exome sequencing is also used to search the causal genes and variants in complex diseases. The successful use of exome sequencing in Mendelian disorders and complex diseases will facilitate the development of personalized genomic medicine.

• Genomics & Informatics
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• v.14 no.3
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• pp.78-84
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• 2016

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.

• Journal of Gastric Cancer
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• v.22 no.4
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• pp.273-305
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• 2022

Gastric cancer (GC) is one of the most common lethal malignant neoplasms worldwide, with limited treatment options for both locally advanced and/or metastatic conditions, resulting in a dismal prognosis. Although the widely used morphological classifications may be helpful for endoscopic or surgical treatment choices, they are still insufficient to guide precise and/or personalized therapy for individual patients. Recent advances in genomic technology and high-throughput analysis may improve the understanding of molecular pathways associated with GC pathogenesis and aid in the classification of GC at the molecular level. Advances in next-generation sequencing have enabled the identification of several genetic alterations through single experiments. Thus, understanding the driver alterations involved in gastric carcinogenesis has become increasingly important because it can aid in the discovery of potential biomarkers and therapeutic targets. In this article, we review the molecular classifications of GC, focusing on The Cancer Genome Atlas (TCGA) classification. We further describe the currently available biomarker-targeted therapies and potential biomarker-guided therapies. This review will help clinicians by providing an inclusive understanding of the molecular pathology of GC and may assist in selecting the best treatment approaches for patients with GC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1693-1698
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• 2015

The heterogeneous nature of lung cancer has become increasingly apparent since introduction of molecular classification. In general, advanced lung cancer is an aggressive malignancy with a poor prognosis. Activating alterations in several potential driver oncogenic genes have been identified, including EGFR, ROS1 and ALK and understanding of their molecular mechanisms underlying development, progression, and survival of lung cancer has led to the design of personalized treatments that have produced superior clinical outcomes in tumours harbouring these mutations. In light of the tsunami of new biomarkers and targeted agents, next generation sequencing testing strategies will be more appropriate in identifying the patients for each therapy and enabling personalized patients care. The challenge now is how best to interpret the results of these genomic tests, in the context of other clinical data, to optimize treatment choices. In genomic era of cancer treatment, the traditional one-size-fits-all paradigm is being replaced with more effective, personalized oncologic care. This review provides an overview of lung cancer genomics and personalized treatment.

• Clinical and Experimental Pediatrics
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• v.61 no.4
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• pp.101-107
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• 2018

Recent advances in genetics have determined that a number of epilepsy syndromes that occur in the first year of life are associated with genetic etiologies. These syndromes range from benign familial epilepsy syndromes to early-onset epileptic encephalopathies that lead to poor prognoses and severe psychomotor retardation. An early genetic diagnosis can save time and overall cost by reducing the amount of time and resources expended to reach a diagnosis. Furthermore, a genetic diagnosis can provide accurate prognostic information and, in certain cases, enable targeted therapy. Here, several early infantile epilepsy syndromes with strong genetic associations are briefly reviewed, and their genotype-phenotype correlations are summarized. Because the clinical presentations of these disorders frequently overlap and have heterogeneous genetic causes, next-generation sequencing (NGS)-based gene panel testing represents a more powerful diagnostic tool than single gene testing. As genetic information accumulates, genetic testing will likely play an increasingly important role in diagnosing pediatric epilepsy. However, the efforts of clinicians to classify phenotypes in nondiagnosed patients and improve their ability to interpret genetic variants remain important in the NGS era.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.34-38
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• 2020

The term dopa-responsive dystonia (DRD) is used to describe a group of neurometabolic disorders, which are characterized by dystonia, and are typically associated with diurnal fluctuations and respond to levodopa treatment. Autosomal dominant DRD (DYT5a, MIM# 128230) is caused by a heterozygous mutation in the GTP cyclohydrolase 1 (GCH1) gene (MIM# 600225). GCH1 encodes an enzyme, which is involved in the biosynthesis of tetrahydrobiopterin, an essential co-factor for tyrosine hydroxylase. Herein, we report the case of a 16-year-old girl who was diagnosed with DYT5a. She exhibited additional unusual clinical features, including intellectual disability, depression, multiple skeletal anomalies, and short stature, which are not commonly observed in patients with DYT5a. The patient harbored a heterozygous missense variant, c.539A>C, p.Gln180Pro, in the GCH1 gene, which was identified by targeted gene panel analysis using next-generation sequencing.