• BMB Reports
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• 제52권4호
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• pp.289-294
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• 2019

The present study evaluated the role of AHNAK in Bartonella henselae infection. Mice were intraperitoneally inoculated with $2{\times}10^8$ colony-forming units of B. henselae Houston-1 on day 0 and subsequently on day 10. Blood and tissue samples of the mice were collected 8 days after the final B. henselae injection. B. henselae infection in the liver of Ahnak-knockout and wild-type mice was confirmed by performing polymerase chain reaction, with Bartonella adhesion A as a marker. The proportion of B. henselae-infected cells increased in the liver of the Ahnak-knockout mice. Granulomatous lesions, inflammatory cytokine levels, and liver enzyme levels were also higher in the liver of the Ahnak-knockout mice than in the liver of the wild-type mice, indicating that Ahnak deletion accelerated B. henselae infection. The proportion of CD4+interferon-${\gamma}$ ($IFN-{\gamma}^+$) and $CD4^+$ interleukin $(IL)-4^+$ cells was significantly lower in the B. henselae-infected Ahnak-knockout mice than in the B. henselae-infected wild-type mice. In vitro stimulation with B. henselae significantly increased $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected wild-type mice, but did not increase $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected Ahnak-KO mice. In contrast, $IL-1{\alpha}$, $IL-1{\beta}$, IL-6, IL-10, RANTES, and tumor necrosis $factor-{\alpha}$ secretion was significantly elevated in the splenocytes obtained from both B. henselae-infected wild-type and Ahnak-knockout mice. These results indicate that Ahnak deletion promotes B. henselae infection. Impaired $IFN-{\gamma}$ and IL-4 secretion in the Ahnak-knockout mice suggests the impairment of Th1 and Th2 immunity in these mice.

• Journal of Gastric Cancer
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• 제23권1호
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• pp.107-145
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• 2023

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

• Journal of Genetic Medicine
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• 제16권2호
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• pp.49-54
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• 2019

Purpose: Potocki-Lupski syndrome (PTLS), is a recently identified, rare genomic disorder. The patients are affected by infantile hypotonia, poor growth and developmental delay. Facial dysmorphism may not be obvious in some patients. PTLS is associated with microduplication at chromosome 17p11.2. In the current study, three Korean patients are reported with their clinical and genetic features. Materials and Methods: The clinical findings of each patient were reviewed. Karyotyping and multiplex ligation-dependent probe amplification (MLPA) analyses were done for genetic diagnoses. Results: All the patients did not have the characteristic dysmorphic features, such as broad forehead, triangular face, asymmetric smile and palpebral fissures. On the other hand, all three patients were affected by variable degree of developmental delay, poor oral intake, failure to thrive, and language development disorders. Chromosome 17p11.2 duplication was identified by conventional karyotyping analysis only in one patient, whereas the other confirmed by MLPA analyses. Conclusion: Delayed development was mostly commonly observed in our patients without distinct dysmorphic facial features. In this respect, genomic screening in patients with developmental delay would identify more cases with PTLS to understand their long-term clinical courses with the development of adequate psychological and rehabilitation education program.

• Journal of Genetic Medicine
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• 제12권1호
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• pp.44-48
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• 2015

Townes-Brocks syndrome (TBS) is a rare genetic disorder characterized by the classic triad of congenital anomalies of the anus, thumbs, and ears, with variable expressivity. Additionally, renal malformations, cardiac anomalies, and endocrine and eye abnormalities can accompany TBS, although less frequently. TBS is inherited in an autosomal dominant fashion; however, about 50% of patients have a family history of TBS and the remaining 50% have de novo mutations. SALL1, located on chromosome 16q12.1, is the only causative gene of TBS. SALL1 acts as a transcription factor and may play an important role in inducing the anomalies during embryogenesis. Clinical features of TBS overlap with those of other multiple anomaly syndromes, such as VACTERL syndrome, Baller-Gerold syndrome, Goldenhar syndrome, cat eye syndrome, and Holt-Oram syndrome. Consequently, there are some difficulties in differential diagnosis based on clinical manifestations. Herein, we report a Korean family with two generations of TBS that was diagnosed based on physical examination findings and medical history. Although the same mutation in SALL1 was identified in both the mother and the son, they displayed different clinical manifestations, suggesting a phenotypic diversity of TBS.

• Journal of Genetic Medicine
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• 제4권1호
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• pp.1-5
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• 2007

Unprecedented amount of genetic information being generated from the result of Human Genome Project (HGP) and advances in genetic research is already forcing changes in the paradigm of health and disease. The ultimate goal of genetic medicine is to use genetic information and technology to develop new ways of treatment or even prevention of the disease on an individual level for 'personalized medicine'. Genetics is play ing an increasingly important role in the diagnosis, monitoring and management of common multifactorial diseases in addition to rare single-gene disorders. While wide range of genetic testing have provided benefits to patients and family, uncertainties surrounding test interpretation, the current lack of available medical options for the diseases, and risks for discrimination and social stigmatization may remain to be resolved. However an increasing number of genetic tests are becoming commercially available, including direct to consumer genetic testing, yet public is often unaw are of their clinical and social implications. The personal nature of information generated by a genetic test, its power to affect major life decisions and family members, and its potential misuse raise important ethical considerations. Therefore appropriate genetic counseling is needed for patient to be informed with the benefits, limitations and risks of genetic tests, prior to informed consent for the tests. Physician also should be familiar with the legal and ethical issues involved in genetic testing to tell patients how w ell a particular genetic risk factor relates with likelihood of disease, and be able to provide appropriate genetic counseling. Genetic counseling become a mandatory requirement as global standard for many genetic testing such as prenatal diagnosis, presymtomatic DNA diagnostic tests and cancer susceptibility gene test for familial cancer syndrome. In oder to meet the challenge of genetic medicine of 21 century in korean health care system, professional education program and certification board for medical genetics specialist including non-MD genetic counselors should be addressed by medical society and regulatory policy of national health insurance reimbursement for genetic counseling to be in place to promote the implementation of clinical genetic service including genetic counseling for proper genetic testing.

• Journal of Genetic Medicine
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• 제11권2호
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• pp.86-90
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• 2014

Smith-Lemli-Opitz syndrome (SLOS) is a rare autosomal recessive disorder caused by 7-dehydrocholesterol reductase deficiency. The characteristic clinical features are syndactyly of the second and third toes, facial dysmorphism, multiple malformations, and intellectual disability. Few cases of SLOS have been reported in Korea. We observed a male patient with SLOS who presented with typical facial features, undescended testes, microcephaly, bilateral syndactyly of the second and third toes, and cardiac defects, including patent ductus arteriosus and atrial septal defect. Mutation analysis of the DHCR7 gene identified compound heterozygous mutations of c.907G>A (p.Gly303Arg) and c.1055G>A (p.Arg352Gln). In a review of the literature, c.1054C>T (p.Arg352Trp) was the most common mutation reported in Far East Asian countries. This report describes the clinical features, biochemical data, molecular characteristics, and clinical outcome of a Korean patient with SLOS.

• Journal of Interdisciplinary Genomics
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• 제3권1호
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• pp.21-24
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• 2021

Purpose: Activating mutations of the calcium-sensing receptor (CASR) are a rare genetic disorder, and result in autosomal dominant hypocalcemia with hypercalciuria (ADHH). ADHH exhibited varying degrees of hypocalcemia. In this study, we report the clinical and molecular characteristics of activating variants in CASR patients diagnosed in Korea. Methods: This study included three patients with activating variants of CASR confirmed by biochemical and molecular analysis of CASR. Clinical and biochemical findings were reviewed chart retrospectively. Mutation analysis of CASR was performed by Sanger sequencing. Results: Subject 1 showed severe symptoms from the neonatal period and had difficulty in controlling the medications that were administered. Subject 2 was identified as having a novel variant of CASR with hypocalcemia and a low parathyroid hormone that were found in the neonatal period. During a course without medication, hypocalcemia occurred suddenly around 2 years of age. Subject 3 was diagnosed with hypoparathyroidism with hypocalcemic seizures starting from the neonatal period. About 4 years without taking medication with any symptom. However, at 10 years old revisited by repetitive hypocalcemic seizure events. Subject 1 and 3, were heterozygous for c.2474A>T (p.Y825F), c.2395G>A (p.E799K) located in the transmembrane domain (TMD) of CASR. Subject 2 was heterozygous for c.403A>C (S430L) located in the extracellular domain (ECD) of CASR. Conclusion: We reported 3 patients who have activating CASR variant with different onset and severity of symptoms. In the future, further study is needed to determine how the protein level according to the location of the mutation of CASR affects the degree of symptoms.

• Journal of Genetic Medicine
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• 제15권2호
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• pp.64-71
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• 2018

Purpose: Overgrowth syndromes are conditions that involve generalized or localized areas of excess growth. In this study, the clinical, molecular, and genetic characteristics of Korean patients with overgrowth syndrome were analyzed. Materials and Methods: We recruited 13 patients who presented with overgrowth syndrome. All patients fulfilled inclusion criteria of overgrowth syndrome. Analysis of the clinical and molecular investigations of patients with overgrowth syndrome was performed retrospectively. Results: Among the 13 patients with overgrowth syndrome, 9 patients (69.2%) were found to have molecular and genetic causes. Among the seven patients with Sotos syndrome (SS), two had a 5q35microdeletion that was confirmed by fluorescent in situ hybridization. In two patients with SS, intragenic mutations including a novel mutation, c.5993T>A (p.M1998L), were found by Sanger sequencing. One patient had one copy deletion of NDS1 gene which was confirmed by multiplex ligation-dependent probe amplification. Among five patients with Beckwith-Wiedemann syndrome, three had aberrant imprinting control regions; 2 hypermethylation of the differentially methylated region of H19, 1 hypomethylation of the differentially methylated region of Kv. In one patient displaying overlapping clinical features of SS, a de novo heterozygous deletion in the chromosomal region 7q22.1-22.3 was found by single nucleotide polymorphism-based microarray. Conclusion: Considering high detection rate of molecular and genetic abnormalities in this study, rigorous investigations of overgrowth syndrome may be an important tool for the early diagnosis and genetic counseling. A detailed molecular analysis of the rearranged regions may supply the clues for the identification of genes involved in growth regulation.

• Journal of Genetic Medicine
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• 제18권2호
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• pp.142-146
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• 2021

Alagille syndrome (AGS) is a rare autosomal dominant inherited disorder, with major clinical manifestations of bile duct paucity, cholestasis, cardiovascular anomaly, ophthalmic abnormalities, butterfly vertebrae, and dysmorphic facial appearance. It is caused by heterozygous mutations in JAG1 or NOTCH of the Notch signaling pathway presenting with variable phenotypic penetrance and involving multiple organ systems. The following case report describes a unique case of a 16-year-old female with AGS who presented with the primary complaint of renovascular hypertension. She had a medical history of ventricular septal defect and polycystic ovary syndrome. The patient had a dysmorphic facial appearance including frontal bossing, bulbous tip of the nose, a pointed chin with prognathism, and deeply set eyes with mild hypertelorism. Stenoocclusive changes of both renal arteries, celiac artery, lower part of the abdominal aorta, and left intracranial artery, along with absence of the left internal carotid artery were found on examination. Whole exome sequencing was performed and revealed a pathologic mutation of JAG1, leading to the diagnosis of AGS. Reverse phenotyping detected butterfly vertebrae and normal structure and function of the liver and gallbladder. While the representative symptom of AGS in most scenarios is a hepatic problem, in this case, the presenting clinical features were the vascular anomalies. Clinical manifestations of AGS are diverse, and this case demonstrates that renovascular hypertension might be in some cases a presenting symptom of AGS.

• Clinical and Experimental Pediatrics
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• 제65권5호
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• pp.230-238
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• 2022

Myocarditis was previously attributed to an epidemic viral infection. Additional harmful reagents, in addition to viruses, play a role in its etiology. Coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis has recently been described, drawing attention to vaccine-induced myocarditis in children and adolescents. Its pathology is based on a series of complex immune responses, including initial innate immune responses in response to viral entry, adaptive immune responses leading to the development of antigen-specific antibodies, and autoimmune responses to cellular injury caused by cardiomyocyte rupture that releases antigens. Chronic inflammation and fibrosis in the myocardium eventually result in cardiac failure. Recent advancements in molecular biology have remarkably increased our understanding of myocarditis. In particular, microRNAs (miRNAs) are a hot topic in terms of the role of new biomarkers and the pathophysiology of myocarditis. Myocarditis has been linked with microRNA-221/222 (miR-221/222), miR-155, miR-10a^*, and miR-590. Despite the lack of clinical trials of miRNA intervention in myocarditis yet, multiple clinical trials of miRNAs in other cardiac diseases have been aggressively conducted to help pave the way for future research, which is bolstered by the success of recently U.S. Food and Drug Administration-approved small-RNA medications. This review presents basic information and recent research that focuses on myocarditis and related miRNAs as a potential novel biomarker and the therapeutics.