• Journal of Genetic Medicine
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• v.15 no.1
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• pp.38-42
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• 2018

WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome is a rare contiguous gene deletion syndrome caused by deleting genes including WT1 and PAX6 genes in 11p13 region, which is characterized by Wilms tumor, aniridia, genitourinary abnormalities, and intellectual disability. We report the clinical and cytogenetic characteristics of one Korean patient with WAGR syndrome. The patient shows bilateral sporadic aniridia and genital anomalies at 2 months of age. A heterozygous 14.5 Mb interstitial deletion of 11p14.3p12 region was detected by array comparative genomic hybridization. At 2 years and 10 months of age, Wilms tumor is found through regularly abdominal ultrasonography and treated by chemotherapy, radiation therapy and surgery.

• Genomics & Informatics
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• v.3 no.4
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• pp.159-165
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• 2005

The Korean Twin Register (n=154,783 pairs) was reported in 2002 as the first nationwide twin study in Korea and the largest study in Asia. The Twin Register has the information of disease outcomes since 1990, and basic clinical and questionnaire data from biennial health examination provided by Korea National Health Service. The author attempted to calculate some of the genetic parameters of cancers in this population. Common cancers in Korea known to have familial aggregation (colon and breast) and cancers of which familial aggregation is unclear (stomach cancer) were examined for their familial recurrence risks. There were 699 stomach cancers, 438 breast and 491 colorectal cancers cases in the twin register between 1991 and 2003. Like-sex twins showed recurrence risks (${\lambda}_{LS}$) of 5.1 (95% CI 3.7-6.9) for stomach cancers, 15.5 (95% CI1 0.9-20.2) for female breast cancers, and 28.1 (95% CI 23.5-34.4) for colon cancers. Colorectal cancers of female like-sex twins show significantly higher familial recurrence risk 40.7 (95% CI 34.6-47.4), suggesting higher genetic contribution in women than in men. The results show increased familial risks compared with previous studies from the same register and are largely compatible with other studies. The data of the Twin Register could be used for estimating population level genetic parameters, as well as base of the various studies.

• Genomics & Informatics
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• v.12 no.4
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• pp.276-282
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• 2014

The disease tuberculosis, caused by Mycobacterium tuberculosis (MTB), remains a major cause of morbidity and mortality in developing countries. The evolution of drug-resistant tuberculosis causes a foremost threat to global health. Most drug-resistant MTB clinical strains are showing resistance to isoniazid and rifampicin (RIF), the frontline anti-tuberculosis drugs. Mutation in rpoB, the beta subunit of DNA-directed RNA polymerase of MTB, is reported to be a major cause of RIF resistance. Amongst mutations in the well-defined 81-base-pair central region of the rpoB gene, mutation at codon 450 (S450L) and 445 (H445Y) is mainly associated with RIF resistance. In this study, we modeled two resistant mutants of rpoB (S450L and H445Y) using Modeller9v10 and performed a docking analysis with RIF using AutoDock4.2 and compared the docking results of these mutants with the wild-type rpoB. The docking results revealed that RIF more effectively inhibited the wild-type rpoB with low binding energy than rpoB mutants. The rpoB mutants interacted with RIF with positive binding energy, revealing the incapableness of RIF inhibition and thus showing resistance. Subsequently, this was verified by molecular dynamics simulations. This in silico evidence may help us understand RIF resistance in rpoB mutant strains.

• Genomics & Informatics
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• v.3 no.3
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• pp.68-73
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• 2005

Pharmacogenomics research requires an intelligent integration of large-scale genomic and clinical data with public and private knowledge resources. We developed a web-based knowledge base for KPRN (Korea Pharmacogenomics Research Network, http://kprn.snubi. org/). Four major types of information is integrated; genetic variation, drug information, disease information, and literature annotation. Eighteen Korean pharmacogenomics research groups in collaboration have submitted 859 genotype data sets for 91 disease-related genes. Integrative analysis and visualization of the large collection of data supported by integrated biomedical path­ways and ontology resources are provided with a user-friendly interface and visualization engine empowered by Generic Genome Browser.

• Genomics & Informatics
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• v.15 no.2
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• pp.69-80
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• 2017

In this study, cytolethal distending toxin (CDT) producer isolates genome were compared with genome of pathogenic and commensal Escherichia coli strains. Conserved genomic signatures among different types of CDT producer E. coli strains were assessed. It was shown that they could be used as biomarkers for research purposes and clinical diagnosis by polymerase chain reaction, or in vaccine development. cdt genes and several other genetic biomarkers were identified as signature sequences in CDT producer strains. The identified signatures include several individual phage proteins (holins, nucleases, and terminases, and transferases) and multiple members of different protein families (the lambda family, phage-integrase family, phage-tail tape protein family, putative membrane proteins, regulatory proteins, restriction-modification system proteins, tail fiber-assembly proteins, base plate-assembly proteins, and other prophage tail-related proteins). In this study, a sporadic phylogenic pattern was demonstrated in the CDT-producing strains. In conclusion, conserved signature proteins in a wide range of pathogenic bacterial strains can potentially be used in modern vaccine-design strategies.

• Journal of Genetic Medicine
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• v.14 no.1
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• pp.23-26
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• 2017

Isolated 3-methylcrotonyl-CoA carboxylase deficiency is an autosomal recessive disorder affecting leucine metabolism; it is one of the most common inborn metabolic diseases detected in newborn screening. Mutations in the genes MCCC1 or MCCC2 cause a defect in the enzyme 3-methylcrotonyl-CoA carboxylase, with MCCC2 mutations being the form predominantly reported in Korea. The majority of infants identified by neonatal screening usually appear to be asymptomatic and remain healthy; however, some patients have been reported to exhibit mild to severe metabolic decompensation and neurologic manifestations. Here we report the clinical features of a patient with asymptomatic 3-methylcrotonyl-CoA carboxylase deficiency and novel heterozygous MCCC1 mutations.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.1-10
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• 2020

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women, which is characterized by the oligo/anovulation, hyperandrogenism (HA) and polycystic ovarian morphology which are diagnostic criteria. PCOS has diverse clinical aspects in addition to those diagnostic criteria including increased risk for cardiovascular diseases, metabolic syndrome, dyslipidemia, type 2 diabetes and impaired fertility. Because of the heterogeneity of the disease, the pathogenesis of the disease has not been elucidated yet. Therefore, there is no cure for the endocrinopathy. HA and insulin resistance (IR) has been considered two major pillars of the pathogenesis of PCOS. Recent advances in animal studies revealed the critical role of neuroendocrine abnormalities in developing PCOS. Several pathways related to neuroendocrine origin have been investigated such as hypothalamus pituitary ovarian axis, hypothalamus pituitary adrenal axis and hypothalamus pituitary adipose axis. This review summarizes the current knowledge about the role of HA and IR in developing PCOS. In addition, we review the results of recent genome wide association studies for PCOS. This new perspective improves our understanding of the role of neuroendocrine origins in PCOS and suggest a novel potential therapeutic target for the treatment of PCOS.

• Genomics & Informatics
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• v.18 no.4
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• pp.38.1-38.9
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• 2020

Chronotype is an important moderator of psychiatric illnesses, which seems to be controlled in some part by genetic factors. Clock genes are the most relevant genes for chronotype. In addition to the roles of individual genes, gene-gene interactions of clock genes substantially contribute to chronotype. We investigated genetic associations and gene-gene interactions of the clock genes BHLHB2, CLOCK, CSNK1E, NR1D1, PER1, PER2, PER3, and TIMELESS for chronotype in 1,293 healthy Korean individuals. Regression analysis was conducted to find associations between single nucleotide polymorphism (SNP) and chronotype. For gene-gene interaction analyses, the quantitative multifactor dimensionality reduction (QMDR) method, a nonparametric model-free method for quantitative phenotypes, were performed. No individual SNP or haplotype showed a significant association with chronotype by both regression analysis and single-locus model of QMDR. QMDR analysis identified NR1D1 rs2314339 and TIMELESS rs4630333 as the best SNP pairs among two-locus interaction models associated with chronotype (cross-validation consistency [CVC] = 8/10, p = 0.041). For the three-locus interaction model, the SNP combination of NR1D1 rs2314339, TIMELESS rs4630333, and PER3 rs228669 showed the best results (CVC = 4/10, p < 0.001). However, because the mean differences between genotype combinations were minor, the clinical roles of clock gene interactions are unlikely to be critical.

• Journal of Genetic Medicine
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• v.15 no.2
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• pp.110-114
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• 2018

Ataxia-telangiectasia (AT; OMIM 208900) is a rare autosomal recessive inherited progressive neurodegenerative disorder, with onset in early childhood. AT is caused by homozygous or compound heterozygous mutations in ATM (OMIM 607585) on chromosome 11q22. The average prevalence of the disease is estimated at 1 of 100,000 children worldwide. The prevalence of AT in the Republic of Korea is suggested to be extremely low, with only a few cases genetically confirmed thus far. Herein, we report a 5-year-old Korean boy with clinical features such as progressive gait and truncal ataxia, both ankle spasticity, dysarthria, and mild intellectual disability. The patient was identified as a compound heterozygote with two novel genetic variants: a paternally derived c.5288_5289insGA p.(Tyr1763*) nonsense variant and a maternally derived c.8363A>C p.(His2788Pro) missense variant, as revealed by next-generation sequencing and confirmed by Sanger sequencing. Based on claims data from the Health Insurance Review and Assessment Service Republic of Korea, we calculated the prevalence of AT in the Republic of Korea to be about 0.9 per million individuals, which is similar to the worldwide average. Therefore, we suggest that multi-gene panel sequencing including ATM should be considered early diagnosis.

• Journal of Genetic Medicine
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• v.16 no.1
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• pp.19-22
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• 2019

The infantile convulsions and choreoathetosis (ICCA) syndrome is defined when two overlapping clinical features of benign familial infantile epilepsy (BFIE) and paroxysmal kinesigenic dyskinesia (PKD) are present in an individual or a family. Since the gene encoding proline-rich transmembrane protein 2 (PRRT2) was first identified in Han Chinese families with PKD, mutations of PRRT2 have additionally been reported in patients with BFIE and ICCA. We attempted to identify the genetic etiology in an ICCA family where the proband, her elder sister, and a maternal male cousin had BFIE, and her mother had PKD. Whole-exome sequencing performed in the proband and her sister and mother identified a novel pathogenic mutation of PRRT2 (c.640delinsCC; p.Ala214ProfsTer11), which was verified by Sanger sequencing. This frameshift PRRT2 mutation located near the genetic hot spot of base 649_650 results in the premature termination of the protein, as do most previously reported mutations in BFIE, ICCA, and PKD.