• Journal of Genetic Medicine
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• v.12 no.1
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• pp.12-18
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• 2015

Malformations of cortical development (MCD) cover a broad spectrum of developmental disorders which cause the various clinical manifestations including epilepsy, developmental delay, and intellectual disability. MCD have been clinically classified based on the disruption of developmental processes such as proliferation, migration, and organization. Molecular genetic studies of MCD have improved our understanding of these disorders at a molecular level beyond the clinical classification. These recent advances are resulted from the development of massive parallel sequencing technology, also known as next-generation sequencing (NGS), which has allowed researchers to uncover novel molecular genetic pathways associated with inherited or de novo mutations. Although an increasing number of disease-related genes or genetic variations have been identified, genotype-phenotype correlation is hampered when the biological or pathological functions of identified genetic variations are not fully understood. To elucidate the causality of genetic variations, in vivo disease models that reflect these variations are required. In the current review, we review the use of NGS technology to identify genes involved in MCD, and discuss how the functions of these identified genes can be validated through in vivo disease modeling.

• Toxicological Research
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• v.20 no.4
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• pp.299-305
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• 2004

Adult periodontitis (AP) is a chronic inflammatory disease whose etiology is not well defined. Some studies suggested that the clinical characteristics of this disease may be in part explained by genetic factors, and some attempts to find genetic markers for this disease were successful. The interleukin-1 (IL-1) gene family as one of genetic factors may influence the expression of adult periodontitis. The aim of present study is to investigate the frequencies of genetic polymorphisms in the IL-1 gene family encoding three genes (IL-1A, IL-1B and IL-1RN) in Korean AP patients and periodontically healthy controls. There were no significant differences in genotype and allele frequencies of these polymorph isms between two groups, respectively. However, -511 polymorphism of IL-1 B gene was significantly associated with mean pocket depth (MPD, mm) value in AP patients (P<0.05). Therefore, our results suggest that -511 polymorphism in the IL-1B gene may be useful as a genetic marker for the severity of AP in Koreans.

• Development and Reproduction
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• v.27 no.2
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• pp.57-65
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• 2023

Kidney disease affects a significant portion of the global population, yet effective therapies are lacking despite advancements in identifying genetic causes. This limitation can be attributed to the absence of adequate in vitro models that accurately mimic human kidney disease, hindering targeted therapeutic development. However, the emergence of human induced pluripotent stem cells (PSCs) and the development of organoids using them have opened up a way to model kidney development and disease in humans, as well as validate the effects of new drugs. To fully leverage their capabilities in these fields, it is crucial for kidney organoids to closely resemble the structure and functionality of adult human kidneys. In this review, we aim to discuss the potential of using human PSCs or adult kidney stem cell-derived kidney organoids to model genetic kidney disease and renal cancer.

• Biomedical Science Letters
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• v.12 no.4
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• pp.311-318
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• 2006

The GJB2 mutation is mostly recessive in non-syndromic hearing loss, but specific mutations display a dominant type and syndromic hearing impairment. Both U54K and R75Q mutations present a dominant type in pedigrees with associated skin disorders. The purpose of this study was to investigate whether two GJB2 mutations can exhibit a dominant-negative effect on the growth abrogation and the gap junctional intercellular communication capacity exerted by wild-type connexin 26. A specific mutant region of GJB2 showed a loss of gap junction activity and a dominant negative effect on wild-type GJB2. The two mutants exerted a dominant-negative effect on the GJIC capacity and have independently effected GJB2 regulated growth of Hela cells; however, they have no dominant-negative growth effect on wild-type GJB2. It is proposed that the different mechanisms of the dominant-negative effect on wild-type GJB2 involve cell growth and GJIC function. This study describes mutations found in Korean deaf patients and that are typical of other east Asian regions.

• BMB Reports
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• v.52 no.4
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• pp.250-258
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• 2019

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective and progressive loss of dopaminergic neurons. Genetic and environmental risk factors are associated with this disease. The genetic factors are composed of approximately 20 genes, such as SNCA, parkin, PTEN-induced kinase1 (pink1), leucine-rich repeat kinase 2 (LRRK2), ATP13A2, MAPT, VPS35, and DJ-1, whereas the environmental factors consist of oxidative stress-induced toxins such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), rotenone, and paraquat. The analyses of their functions and mechanisms have provided important insights into the disease process, which has demonstrated that these factors cause oxidative damage and mitochondrial dysfunction. The most invaluable studies have been performed using disease model organisms, such as mice, fruit flies, and worms. Among them, Drosophila melanogaster has emerged as an excellent model organism to study both environmental and genetic factors and provide insights to the pathways relevant for PD pathogenesis, facilitating development of therapeutic strategies. In this review, we have focused on the fly model organism to summarize recent progress, including pathogenesis, neuroprotective compounds, and newer approaches.

• Journal of Chest Surgery
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• v.14 no.1
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• pp.87-90
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• 1981

Genetic and environmental factors are the two areas which have received attention in the etiology of congenital cardiac malformation. Genetic factor in many types of congenital heart disease have not been clearly delineated. Congenital heart diseases are a heterogenous category of developmental anomalies, representing in most cases the multifactorial inheritance of threshold characters, the expression of which is the product of a genetic - environmental interaction. Recently we experienced three pairs of congenital heart disease in siblings including ventricular septal defects in twin.

• Animal cells and systems
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• v.14 no.1
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• pp.31-36
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• 2010

The pinewood nematode Bursaphelenchus xylophilus causes pine wilt disease and is a serious economic concern for the forest industry of South Korea. To achieve effective control with limited resources, it is necessary to clarify the transmission routes and mechanisms of dispersal of this organism. Highly polymorphic and easy-to-use molecular markers can be used for investigating this aspect. In this study, we evaluated the usefulness of amplified fragment length polymorphisms (AFLPs) for investigating the genetic variations of B. xylophilus and related individuals from China, Japan, and South Korea. The AFLP patterns obtained in our study were similar to the microsatellite patterns reported in a previous study; our AFLP patterns indicated high genetic variability and cryptic genetic structure, but did not indicate any peculiar geographic structure. Moreover, the genetic distances between individuals suggested that the Korean population was affected to a greater extent by the Chinese population than the Japanese population. Further, the gene flow among the related species appeared to be limited; however, there may be also the possibility of genetic introgression among species. These results confirm the usefulness of AFLPs for understanding the epidemiology of pine wilt disease, thereby contributing to the effective control of this disease.

• Childhood Kidney Diseases
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• v.27 no.2
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• pp.70-75
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• 2023

Dent disease is a rare inherited kidney tubulopathy caused by mutations in either the CLCN5 (Dent disease 1) or OCRL1 (Dent disease 2) genes, and which is often underdiagnosed in practice. A diagnosis is clinically suspected in patients with low-molecular-weight proteinuria, hypercalciuria, and one of the following: hematuria, nephrolithiasis, nephrocalcinosis, hypophosphatemia, or chronic kidney disease. Inheritance is X-linked recessive, meaning, these symptoms are generally only found in males; female carriers may have mild phenotypes. Genetic testing is only a method to confirm the diagnosis, approximately 25% to 35% of patients have neither the CLCN5 nor OCRL1 pathogenic variants (Dent disease 3), making diagnosis more challenging. The genotype-phenotype correlations are not evident with the limited clinical data available. As with many other genetic diseases, the management of patients with Dent disease concentrates on symptom relief rather than any causative process. The current treatments are mainly supportive to reduce hypercalciuria and prevent nephrolithiasis. Chronic kidney disease progresses to end-stage between the ages of the third to fifth decades in 30% to 80% of affected males. In this review, we aimed to summarize the literature on Dent disease and reveal the clinical characteristics and molecular basis of Korean patients with Dent disease.

• Childhood Kidney Diseases
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• v.28 no.1
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• pp.8-15
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• 2024

With the rapid evolution of diagnostic tools, particularly next-generation sequencing, the identification of genetic diseases, predominantly those with pediatric-onset, has significantly advanced. However, this progress presents challenges that span from selecting appropriate tests to the final interpretation of results. This review examines various genetic testing methodologies, each with specific indications and characteristics, emphasizing the importance of selecting the appropriate genetic test in clinical practice, taking into account factors like detection range, cost, turnaround time, and specificity of the clinical diagnosis. Interpretation of variants has become more challenging, often requiring further validation and significant resource allocation. Laboratories primarily classify variants based on the American College of Medical Genetics and Genomics and the Association for Clinical Genomic Science guidelines, however, this process has limitations. This review underscores the critical role of clinicians in matching patient phenotypes with reported genes/variants and considering additional factors such as variable expressivity, disease pleiotropy, and incomplete penetrance. These considerations should be aligned with specific gene-disease characteristics and segregation results based on an extended pedigree. In conclusion, this review aims to enhance understanding of the complexities of clinical genetic testing, advocating for a multidisciplinary approach to ensure accurate diagnosis and effective management of rare genetic diseases.

• Journal of Genetic Medicine
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• v.9 no.2
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• pp.67-72
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• 2012

The generation of induced pluripotent stem cells (iPSCs) derived from patients' somatic cells provides a new paradigm for studying human genetic diseases. Human iPSCs which have similar properties of human embryonic stem cells (hESCs) provide a powerful platform to recapitulate the disease-specific cell types by using various differentiation techniques. This promising technology has being realized the possibility to explore pathophysiology of many human genetic diseases at the molecular and cellular levels. Furthermore, disease-specific human iPSCs can also be used for patient-based drug screening and new drug discovery at the stage of the pre-clinical test in vitro. In this review, we summarized the concept and history of cellular reprogramming or iPSC generation and highlight recent progresses for disease modeling using patient-specific iPSCs.