• 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.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.5
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• pp.479-486
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• 2019

Progressive familial intrahepatic cholestasis (PFIC) is a group of severe genetic disorders, inherited in an autosomal recessive manner, causing cholestasis of hepatocellular origin, later progressing to biliary cirrhosis and liver failure. This is the first report of PFIC type 1 with novel compound heterozygous mutations in Korea. The patient was presented with intrahepatic cholestasis, a normal level of serum ${\gamma}-glutamyl$ transferase, steatorrhea, and growth failure. Genetic testing of this patient revealed novel compound heterozygous mutations (p.Glu585Ter and p.Leu749Pro) in the ATP8B1 gene. After a liver transplantation at age 19 months, the patient developed severe post-transplant steatohepatitis.

• Childhood Kidney Diseases
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• v.25 no.2
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• pp.128-132
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• 2021

Morning glory syndrome (MGS) is a rare congenital optic disc anomaly with a characteristic fundal finding with severe visual impairment. It may occur in association with various systemic manifestations, even though most of the reported cases were isolated. A 6-year-old male visited the nephrology clinic with a history of microscopic hematuria and at the age of 12 years, he was diagnosed thin glomerular basement membrane nephropathy by kidney biopsy. After the following years, the patient had progressive deterioration of visual acuity, and diagnosed as MGS. Whole Exome Sequencing of this patient and his mother revealed heterozygous COL4A4 mutations [c.81_86del (p.Ile29_Leu30del)]. It is more reasonable to consider MGS seen in this patient as a coincidental finding of autosomal dominant Alport syndrome. To our knowledge, this case represents the first case report of autosomal dominant Alport syndrome associated with MGS.

• Journal of Genetic Medicine
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• v.18 no.2
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• pp.147-151
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• 2021

The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) (Online Mendelian Inheritance in Man #603736) is a rare autosomal dominant disorder and clinically features blepharophimosis with ptosis, a mask-like facial appearance, cryptorchidism, congenital heart defect, long thumbs/great toes, and thyroid dysfunction. The etiology of SBBYSS has been shown to be due to heterozygous KAT6B gene mutation. Here we report a case of a neonate with SBBYSS identified a novel mutation in KAT6B gene. The patient showed typical dysmorphic facies, cryptorchidism with micropenis, overriding fingers, and long thumbs and toes at birth. He had also hypothyroidism, large atrial septal defect, and sensorineural hearing loss. The next generation sequencing identified a heterozygous novel variant, c.5206C>T (p.Gln1736Ter) in KAT6B gene. At the 9 months of age, he underwent patch closure for atrial septal defect. Until the 12-month follow-up, he was under-developed.

• Proceedings of the Korean Environmental Health Society Conference
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• 2003.06a
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• pp.187-191
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• 2003

In this study, biomonitoring methods were developed to measure BTEXs exposure level in the air, metabolites of benzene and toluene in human urine, individual susceptibility markers in human blood for evaluation of the health effects about environmental pollution. We have also performed a small-scaled molecular epidemiology study on residents in Chuncheon and workers in workplace for these method applications. The workers in workplace were surveyed as study areas, and the residents in Chuncheon which is in the suburban area were surveyed as comparative areas in this study. Actually, 31 workers in as target group and 33 residences in as control group this epidemiological study. The results obtained from this study were as follows: 1. Benzene is a well-known carcinogen, it's median concentrations were 0.00024∼0.02057ppm at suburban area and 0.002∼00.654ppm at work place, These benzene concentrations were not exceed the OSHA(Occupational Safety and Health Administration) threshold benzene level of 1ppm in the states. 2. Metabolites product of benzene(t,t-Muconic Acid) and toluene(Hippuric Acid) were not significant both in suburban and workplace area. The median concentration of t,t-MA and HA were 0.0122, 1.44277g/g creatinine, respectively. 3. In the case of individual susceptibility markers as CYPlAl, 41.8% of them has homozygous wild type(W) and who has heterozygous variant type(H) was 35.4% and 22.8% of homozygous variant type(M) genetic type. In the case of CYP2E1, 62.82% of them has homozygous wild type(D) type, 34.62% of each has heterozygous variant type (DC) and 2.56% of them has homozygous variant type (CC). Who doesn't have GSTM1 gene was 46.25% and who has GSTM1 gene was 53.75％. Who doesn't have GSTT1 gene was 40.0％ in study groups and who has GSTT1 gene was 60.0%. Who has W genetic type, which is homozygous wild type of GSTP1, was 69.18% and H genetic type, which is heterozygous variant type was 28.4%. M genetic type which is homozygous variant type was 2.4%. 4. Concentration differences of metabolites such as t,t-MA and HA in urine, which is generated by individual susceptibility marker of GSTM1, GSTT1, GSTP1 gene of Phase I and CYP1A1, CYP2E1 gene of Phase II, was examined. As a result, GSTP1 and GSTM1 indicate slight differences depend on the amount of metabolites in urine, it was not statistically significant.

• Journal of Genetic Medicine
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• v.5 no.2
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• pp.131-135
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• 2008

Classical galactosemia is an autosomal recessive disorder of galactose metabolism, caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). Buildup of galactose-1-phosphate is toxic at high levels and can damage the liver, brain, eyes, and other vital organs. The case presented here was that of an 11-day-old female infant who had elevated galatose levels upon initial neonatal screening test with persistent cholestatic jaundice, coagulopathy, and hepatomegaly. The patient was transferred due to aggravation of clinical symptoms including bleeding and jaundice. She had a delayed galactose free diet because of an inappropriate diagnosis. We quickly provided her with a lactose/galactose-restricted diet as per her final diagnosis. Clinical and laboratory results were improved after a few days of treatment. For confirmatory testing for classical galactosaemia, we simultaneously analyzed for GALT enzyme activity and allele-specific PCR/fragments for seven mutations and two polymorphisms in the GALT gene. We were able to find several GALT-deficient and compound heterozygous mutations of the GALT gene.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.619-624
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• 2013

Background: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable. Aim: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk. Methods: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs). Results: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253). Conclusion: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.234-247
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• 2021

We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the Erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.

• Proceedings of the Zoological Society Korea Conference
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• 1998.10b
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• pp.313.2-313
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• 1998

No Abstract, See Full Text

• Genomics & Informatics
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• v.9 no.3
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• pp.138-141
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• 2011

Here, we report a computer program written in Python, which phases SNP genotypes and infers inherited deletions based on the pattern of Mendelian inheritance within a trio pedigree. When tiered trio genotypes that encompass three generations are available, it narrows a recombination event down to a region between two consecutive heterozygous markers. In addition, the phase information that is inferred from the upper trio that is formed by one of the parents and grandparents can be propagated to phase the genotypes of the lower trio that is formed by the parents and an offspring.