• Neonatal Medicine
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• v.16 no.1
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• pp.71-75
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• 2009

There are few cases of partial trisomy of 9q, known as partial 9q trisomy syndrome with low birth weight, microcephaly, hypotelorism, beaked nose, small lip, long finger, hypertrophic pyloric stenosis, ventricular septal defect, and mental retardation. We report partial trisomy of 9q derived from a paternal chromosome, which has different features of other syndromes, including prematurity, atrial and ventricular septal defect, patent ductus arteriosus, persistent left superior vena cava, congenital hydronephrosis, and scrotal hernia.

• Clinical and Experimental Pediatrics
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• v.45 no.4
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• pp.540-544
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• 2002

Rett syndrome is an X-linked dominant, progressive neurodevelopmental disorder, with a prevalence estimated to be one in 10,000-15,000 girls, which is thought to be the second most common genetic causes of mental retardation in females after Down syndrome. Patients with classic Rett syndrome show an apparently normal neonatal period, followed by developmental regression and deceleration of head growth, accompanied by gradual loss of speech and purposeful hand use, and development of microcephaly, seizures, autism, ataxia, intermittent hyperventilation and stereotypic hand movements. After regression between infancy and the fifth year of life, the clinical course stabilizes and patients usually survive into adulthood. It was recently discovered that Rett syndrome is caused by mutations in the methyl-CpG binding protein 2(MECP2) gene. Diagnosis of Rett syndrome is clinically difficult before three years of age, especially in atypical cases, but molecular analysis of the MECP2 gene could assist correct diagnosis in some patients. Recently, we diagnosed a case of Rett syndrome in a two year-old girl by mutational analysis of the MECP2 gene and want to report this case with brief review of literature.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.14-18
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• 2016

Pediatric epilepsy can be caused by various conditions, including specific syndromes. 1p36 deletion syndrome is reported in 1 in 5,000-10,000 newborns, and its characteristic clinical features include developmental delay, mental retardation, hypotonia, congenital heart defects, seizure, and facial dysmorphism. However, detection of the terminal deletion in chromosome 1p by conventional G-banded karyotyping is difficult. Here we present a case of epilepsy with profound developmental delay and characteristic phenotypes. A 7-year-and 6-month-old boy experienced afebrile generalized seizure at the age of 5 years and 3 months. He had recurrent febrile seizures since 12 months of age and showed severe global developmental delay, remarkable hypotonia, short stature, and dysmorphic features such as microcephaly; small, low-set ears; dark, straight eyebrows; deep-set eyes; flat nasal bridge; midface hypoplasia; and a small, pointed chin. Previous diagnostic work-up, including conventional chromosomal analysis, revealed no definite causes. However, array-comparative genomic hybridization analysis revealed 1p36 deletion syndrome with a 9.15-Mb copy loss of the 1p36.33-1p36.22 region, and fluorescence in situ hybridization analysis (FISH) confirmed this diagnosis. This case highlights the need to consider detailed chromosomal study for patients with delayed development and epilepsy. Furthermore, 1p36 deletion syndrome should be considered for patients presenting seizure and moderate-to-severe developmental delay, particularly if the patient exhibits dysmorphic features, short stature, and hypotonia.

• Journal of Microbiology and Biotechnology
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• v.30 no.11
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• pp.1651-1658
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• 2020

Since Zika virus (ZIKV) was first detected in Uganda in 1947, serious outbreaks have occurred globally in Yap Island, French Polynesia and Brazil. Even though the number of infections and spread of ZIKV have risen sharply, the pathogenesis and replication mechanisms of ZIKV have not been well studied. ZIKV, a recently highlighted Flavivirus, is a mosquito-borne emerging virus causing microcephaly and the Guillain-Barre syndrome in fetuses and adults, respectively. ZIKV polyprotein consists of three structural proteins named C, prM and E and seven nonstructural proteins named NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 in an 11-kb single-stranded positive sense RNA genome. The function of individual ZIKV genes on the host innate immune response has barely been studied. In this study, we investigated the modulations of the NF-κB promoter activity induced by the MDA5/RIG-I signaling pathway. According to our results, two nonstructural proteins, NS2A and NS4A, dramatically suppressed the NF-κB promoter activity by inhibiting signaling factors involved in the MDA5/RIG-I signaling pathway. Interestingly, NS2A suppressed all components of MDA5/RIG-I signaling pathway, but NS4A inhibited most signaling molecules, except IKKε and IRF3-5D. In addition, both NS2A and NS4A downregulated MDA5-induced NF-κB promoter activity in a dosedependent manner. Taken together, our results suggest that NS2A and NS4A signifcantly antagonize MDA5/RIG-I-mediated NF-κB production, and these proteins seem to be controlled by different mechanisms. This study could help understand the mechanisms of how ZIKV controls innate immune responses and may also assist in the development of ZIKV-specific therapeutics.

• Genomics & Informatics
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• v.14 no.3
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• pp.104-111
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• 2016

Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family. In this study, we performed molecular docking analysis of these drugs against nonstructural 3 (NS3) protein of ZIKV. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of ZIKV infection. Amongst these four drugs, berberine has shown highest binding affinity of -5.8 kcal/mol and it is binding around the active site region of the receptor. Based on the properties of berberine, more similar compounds were retrieved from ZINC database and a structure-based virtual screening was carried out by AutoDock Vina in PyRx 0.8. Best 10 novel drug-like compounds were identified and amongst them ZINC53047591 (2-(benzylsulfanyl)-3-cyclohexyl-3H-spiro[benzo[h]quinazoline-5,1'-cyclopentan]-4(6H)-one) was found to interact with NS3 protein with binding energy of -7.1 kcal/mol and formed H-bonds with Ser135 and Asn152 amino acid residues. Observations made in this study may extend an assuring platform for developing anti-viral competitive inhibitors against ZIKV infection.

• Archives of Plastic Surgery
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• v.34 no.4
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• pp.528-530
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• 2007

Purpose: Holoprosencephaly(HPE) is a rare developmental defect due to incomplete cleavages of the prosencephalon during the third week of fetal development. Chromosomal anomalies, genetic syndrome, teratogen, or genetic disorder of non-syndromic HPE are usually accepted as etiology. The consequences of prechordal mesoderm defect are varying degrees of deficit of midline facial development, especially the median nasal process(premaxilla), and incomplete morphogenesis of the forebrain. We experienced a case of lobar HPE with complete cleft lip and palate. Methods: A female newborn infant was born at $38^{+6}$ weeks' gestational age via NSVD. The infant's birth weight was 3.6 kg, height 52 cm, and head circumference 32.5 cm, showing microcephaly, flat nose, median complete cleft lip & palate, and hypotelorism, along with defects of midfacial development including losses of premaxilla, philtrum, nasal septum, and columella. Results: There were no specific findings noted from the head and neck X-ray and tests for endocrine and metabolic disorders, but clinical characteristics of midface and dysgenesis corpus callosum on brain MRI were seen, so that this case was diagnosed with HPE. Conclusion: HPE is divided into three categories of alobar, semilobar, and lobar prosencephaly according to the degree of cerebral hemisphere separation. Assesment of patient's brain abnormality and malformation is essential in determining the extent and benefit of surgical intervention. This case was included in the lobar type HPE which shows relatively good prognosis compared with other types and reconstruction of median complete cleft lip & palate and midfacial defects will be performed.

• Neonatal Medicine
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• v.15 no.1
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• pp.89-93
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• 2008

Duplication of chromosome 12p has been rarely reported and are thought to be associated with congenital malformations and impaired development. We report a baby boy born with multiple dysmorphic features and congenital malformations. His karyotype was 46,XY, add(12)(p13.3). He has suffered from intrauterine growth restriction at birth. He showed abnormal cranio-facial findings such as microcephaly, hypognathia, clepft palate and low set ear. He presented with absence of uvula, micropenis and rocker bottom features of both feet, congenital heart disease, poor corticomedullary differentiation of kidney, and sensorineuronal hearing loss. We have been follow up him for seizure disorder and delayed development at out patient department.

• Journal of Genetic Medicine
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• v.11 no.2
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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 Genetic Medicine
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• v.18 no.1
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• pp.48-54
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• 2021

Genetic imbalances are a major cause of congenital and developmental abnormalities. We report the first case of a 3p26 microdeletion and 5q35.2q35.3 microduplication in a newborn with multiple congenital anomalies evaluated using chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH). The patient was born at 30 weeks and 2 days of gestation with a body weight of 890 g. He had symmetric intrauterine growth restriction, microcephaly, facial dysmorphism (hypertelorism, blepharophimosis, mild low-set ears, high-arched palate, and micrognathia), and right thumb polydactyly. Echocardiography revealed an atrial septal defect and patent ductus arteriosus. Furthermore, CMA revealed a concurrent microdeletion in 3p26 and a microduplication in 5q35.2q35.3. FISH analysis showed that these genetic changes resulted from a translocation mutation between chromosomes 3 and 5. The patient's mother had mild intellectual disability, short stature, and facial dysmorphism, while his father had a normal phenotype. However, parental FISH analysis revealed that the asymptomatic father carried a balanced translocation of chromosomes 3p26 and 5q35. CMA and FISH tests are useful for diagnosing neonates with multiple congenital abnormalities. Further parental genetic investigation and proper genetic counseling are necessary in cases of chromosomal abnormalities inherited from parental balanced translocations.

• Journal of Genetic Medicine
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• v.19 no.2
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• pp.105-110
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• 2022

The microdeletion syndrome of chromosome 2p15p16.1 (MIM: 612513) is an extremely rare contiguous gene deletion syndrome. Microdeletions of varying sizes in the 2p15-16.1 region are associated with developmental delay, intellectual disability, autism spectrum disorder, hypotonia, and craniofacial dysmorphism. Previous studies have identified two critical regions: the proximal 2p15 and distal 2p16.1 regions. BCL11A, PAPOLG, and REL genes play crucial roles in patients with 2p16.1 microdeletion. To our knowledge, only 39 patients have been reported as having 2p15p16.1 microdeletion syndrome. Here, we present another patient with 2p15p16.1 microdeletion syndrome. A nine-month-old boy was referred to our clinic for the psychomotor delay, facial dysmorphism, and congenital hypothyroidism. During his follow-up visits, he was diagnosed with global developmental delay, intellectual disability, abnormal behavior, hypotonia, microcephaly, and abnormal electroencephalography. Using a chromosomal microarray for genetic analysis, a novel, de novo, 622 kb microdeletion of 2p16.1 was identified as one of the critical regions of the 2p15p16.1 microdeletion syndrome. This is the first case of its kind in Korea. We have discussed our case and literature reviews to clarify the relationship between the genes involved and clinical phenotypes in 2p15p16.1 microdeletion syndrome.