• Genomics & Informatics
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• v.2 no.2
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• pp.81-85
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• 2004

To examine whether the IL-1A (-889) polymorphism associates with a risk for Alzheimer's disease (AD) and acts interactively with the apolipoprotein (APOE) $\epsilon$4 in the development of AD, we performed genotype analyses of the IL-1A and the APOE of the 102 Korean AD patients and 200 Korean non-demented controls. We failed to detect a significant difference in genotypic and allelic frequencies of IL-1A between the AD group and control group. No overexpression of the IL-1A C/T genotype and IL-1A T allele was found when we analyzed the late-onset and early-onset patients, separately. There was no significant genetic interaction between IL-1A polymorphism and the APOE polymorphism. I n conclusion, the IL-1A polymorphism did not contribute to the development of AD independently or interactively with the APOE $\epsilon$4 allele in Koreans.

• Journal of Genetic Medicine
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• v.9 no.1
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• pp.1-10
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• 2012

About 7% of all breast cancer (BC) cases result from a genetic predisposition, and approximately 1,000 patients develop hereditary BC (HBC) every year in Korea. BRCA1 and BRCA2 are the primary genes underlying HBC. The average cumulative risks in BRCA1 mutation carriers at 70 years of age are 65% (95% confidence interval 44-78%) for BC and 39% (18-54%) for ovarian cancer (OC). The corresponding estimates for BRCA2 are 45% (31-56%) and 11% (2.4-19%), respectively. The penetrance of BRCA mutations is not the same between patients and can depend on factors such as race and birth-cohort. The Korean Hereditary Breast Cancer (KOHBRA) study is a large prospective nationwide study that includes 39 participating centers. Between May 2007 and May 2010, the first phase of the KOHBRA study was planned and fulfilled successfully. The primary aim of phase I was to estimate the prevalence of BRCA1/2 mutations and OC among a high-risk group of patients with HBC and their families. According to data collected during phase I of the study, the prevalence and penetrance of BRCA mutations were comparable to corresponding data from Western countries. For the second phase of the KOHBRA study, we are currently investigating a Korean BRCA mutation prediction model, prognostic factors in BRCA-related BC, environmental/genetic modifiers, and implementing a genetic counseling network. The final goal of the KOHBRA study is to create clinical practice guidelines for HBC in Korea. In this article, I review the genetics of HBC, summarize the characteristics of Korean HBC, and discuss current and future HBC research in Korea.

• Journal of Genetic Medicine
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• v.9 no.1
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• pp.42-46
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• 2012

Short-chain acyl-CoA dehydrogenase deficiency (SCADD; OMIM # 201470) is an autosomal recessive inborn error of mitochondrial fatty acid ${\beta}$-oxidation, presenting with a variety of clinical signs and symptoms. Developmental delay, hypertonia or hypotonia, ketotic hypoglycemia, and epilepsy are most frequently reported. In general, patients diagnosed through newborn screening have shown normal growth and development in contrast to those diagnosed as a result of clinically initiated evaluations. Here, the case of an asymptomatic Korean newborn with SCADD identified by tandem mass spectrometry is reported. The patient showed an elevated concentration of butyrylcarnitine detected on newborn screening. Urinary excretion of ethylmalonic acid was elevated by urine organic acid analysis. To confirm the diagnosis of SCADD, a direct sequencing analysis of 10 coding exons and the exon-intron boundaries of the ACADS gene were performed. Genetic analysis of ACADS showed the following novel compound heterozygous missense mutations: c.277C>A (p.Leu93Ile) on exon3 and c.682G>A (p.Glu288Lys) on exon6. These results will provide further evidence of mutational heterogeneity for SCADD.

• Journal of Genetic Medicine
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• v.9 no.1
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• pp.11-16
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• 2012

Purpose: To determine a method to improve the efficacy and accuracy of preimplantation genetic diagnosis (PGD) - polymerase chain reaction (PCR), we compared hot start PCR and conventional multiplex nested PCR. Materials and Methods: This study was performed with single lymphocyte isolated from whole blood samples that were obtained from two couples with osteogenesis imperfecta (OI). We proceeded with conventional multiplex nested PCR and hot start PCR in which essential reaction components were physically removed, and we compared the amplification rate, allele dropout rate and nonspecific products. Afterward, we used selective method for PGD. Results: In the two couples, the respective amplification rate were 93.5% and 80.0% using conventional multiplex nested PCR and 95.5% and 92.0% using hot start PCR. The respective mean allele dropout rates for the two couples were 42.0% and 14.0% with conventional multiplex nested PCR and 36.0% and 6.0% with hot start PCR. Conclusion: The results demonstrate that the hot start PCR procedure provides higher amplification rates and lower allele dropout rate than the conventional method and that it decreased the nonspecific band in multiplex nested PCR. The hot start method is more efficient for analyzing a single blastomere in clinical PGD.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.16-20
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• 2020

Purpose: Duodenal atresia (DA) and atrioventricular septal defect (AVSD) are well known ultrasonographic findings associated with Down syndrome. The risk of Down syndrome in fetuses with these anomalies has been reported as 30% to 40%. However, on the basis of our clinical experience, the risk of Down syndrome of DA may be lower in Korean population. To clarify this issue, we compared the risk of Down syndrome between cases with DA and AVSD. Materials and Methods: The study population consisted of neonates who were confirmed as DA or AVSD by postnatal diagnosis. Postnatal diagnosis was made by surgery, postnatal echocardiography, or autopsy. Medical record was reviewed retrospectively. Results: A total of 213 neonates with DA or AVSD were included: 67 cases with DA and 146 cases with AVSD. The risk of Down syndrome was 4.5% (3/67) in DA vs. 29.5% (43/146) in AVSD. When confining analysis to those whose karyotyping were not performed during antenatal period, the risk of Down syndrome were 7.9% (3/38) in DA and 35.4% (35/99) in AVSD. Conclusion: The risk of Down syndrome in cases with DA was much lower in Korean population than previously reported risk in the literature. The significance of some antenatal sonographic markers for Down syndrome may be different according to ethnicity.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.43-46
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• 2020

The Shprintzen-Goldberg syndrome (SGS) is an extremely rare genetic disorder caused by heterozygous variant in SKI. SGS is characterized by neurodevelopmental impairment with skeletal anomaly. Recognition of SGS is sometimes quite challenging in practice because it has diverse clinical features involving skeletal, neurological, and cardiovascular system. Here we report a case of a 6-month-old boy who initially presented with developmental delay and marfanoid facial features including prominent forehead, hypertelorism, high arched palate and retrognathia. He showed motor developmental delay since birth and could not control his head at the time of first evaluation. His height was above 2 standard deviation score. Arachnodactyly, hypermobility of joints, skin laxity, and pectus excavatum were also noted. Sequencing for FBN1 was negative, however, a novel missense variant, c.350G>A in SKI was identified by sequential whole exome sequencing. To our knowledge, this is the first case with SGS with phenotypic features of SGS overlapping with those of the Marfan syndrome, diagnosed by next generation sequencing in Korea.

• Journal of Nutrition and Health
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• v.35 no.10
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• pp.1053-1059
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• 2002

In post-genome period, the technique for identifying gene expression has been changed to high throughput screening. In the field of molecular nutrition, the need for this technique to clarify molecular function of the specific nutrient is essential. In this study, we have tested the zinc-regulated gene expression in zinc-deficient U937 cells, using cDNA microarray which is the cutting-edge technique to screen large numbers of gene expression simultaneously. The study result can be used for the preliminary gene screening data for clarifying, using monocyte U937 cell line, molecular Zn aspect in atherosclerosis. U937 cells were cultured in Zn-adequate (control, 12 $\mu$M Zn) or Zn-deficient (experimental, 0 $\mu$M Zn) ESMI media during 2 days, respectively. Cells were harvested and RNA was extracted. Total RNA was reverse-transcriptinized and synthesized cDNA probe labeled with Cy-3. fluorescent labeled cDNA probe was applied to microarray slide for hybridization slide, and after then, the slide was scanned using fluorescence scanner. ‘Highly expressed genes’ in Zn-deficient U937 cells, comparing to Zn-adequate group, are mainly about the genes for motility protein, immune system protein, oncogene and tumor suppressor and ‘Less highly expressed genes’ are about the genes for transcription, apoptosis associated protein, cell cycle, and several basic transcription factors. The results of this preliminary study imply the effectiveness of cDNA microarray for expression profiling of a singly nutrient deficiency, specially Zn. Furthur study, using tailored-cDNA array and capillary endothelial cell lines, would be beneficial to clarify molecular Zn function, more in detail.

• Annals of Laboratory Medicine
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• v.38 no.6
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• pp.524-529
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• 2018

Background: An increase in neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular injury. Diabetic nephropathy causes typical changes in the kidney, characterized by glomerulosclerosis and eventual tubular damage. We validated the usefulness of plasma NGAL (pNGAL) as a biomarker of tubular damage in patients with diabetic nephropathy. Methods: We included 376 patients with diabetes mellitus (260 patients with chronic renal insufficiency who had not received hemodialysis and 116 hemodialyzed due to diabetic nephropathy) and 24 healthy controls. Patients with chronic renal insufficiency were divided into three groups according to urinary albumin excretion (UAE) levels. pNGAL levels were measured using the Triage NGAL test (Alere, San Diego, CA, USA) and were compared between groups. We also examined whether pNGAL level was related to the degree of albuminuria and cystatin C-based glomerular filtration rate (GFR). Results: Mean pNGAL levels of the healthy controls, chronic renal insufficiency patients with diabetes mellitus, and hemodialyzed patients were $61.9{\pm}5.3ng/mL$, $93.4{\pm}71.8ng/mL$, and $1,536.9{\pm}554.9ng/mL$, respectively. pNGAL level increased significantly in patients with severe albuminuria (P <0.001) and had a moderate correlation with the degree of albuminuria (r=0.467; P <0.001) and GFR (r=0.519; P <0.001). Multivariate regression analysis showed that the pNGAL level was associated with tubular damage independent of patient age, sex, and GFR. Conclusions: pNGAL level independently reflects the degree of tubular damage in patients with diabetic nephropathy. Measurement of pNGAL, combined with UAE, would enable simultaneous, highly reliable assessments of tubular damage for such patients.

• Genes and Genomics
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• v.40 no.12
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• pp.1269-1277
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• 2018

Bcl2-associated athanogene 3 (BAG3) mutations have been reported to cause the myofibrillar myopathy (MFM) which shows progressive limb muscle weakness, respiratory failure, and cardiomyopathy. Myopathy patients with BAG3 mutation are very rare. We described a patient showing atypical phenotypes. We aimed to find the genetic cause of Korean patients with sensory motor polyneuropathy, myopathy and rigid spine. We performed whole exome sequencing (WES) with 423 patients with sensory motor polyneuropathy. We found BAG3 mutation in one patient with neuropathy, myopathy and rigid spine syndrome, and performed electrophysiological study, whole body MRI and muscle biopsy on the patient. A de novo heterozygous p.Pro209Leu (c.626C>T) mutation in BAG3 was identified in a female myopathy. She first noticed a gait disturbance and spinal rigidity at the age of 11, and serum creatine kinase levels were elevated ninefolds than normal. She showed an axonal sensory-motor polyneuropathy like Charcot-Marie-Tooth disease (CMT), myopathy, rigid spine and respiratory dysfunction; however, she did not show any cardiomyopathy, which is a common symptom in BAG3 mutation. Lower limb MRI and whole spine MRI showed bilateral symmetric fatty atrophy of muscles at the lower limb and paraspinal muscles. When we track traceable MRI 1 year later, the muscle damage progressed slowly. As far as our knowledge, this is the first Korean patient with BAG3 mutation. We described a BAG3 mutation patient with atypical phenotype of CMT and myopathy, and those are expected to broaden the clinical spectrum of the disease and help to diagnose it.

• Journal of Genetic Medicine
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• v.15 no.2
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• pp.102-106
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• 2018

Aggrecan is a proteoglycan in the extracellular matrix of growth plate and cartilaginous tissues. Aggrecanopathy has been reported as a genetic cause not only for severe skeletal dysplasia but also for autosomal dominant short stature with normal to advanced bone age. We report a novel heterozygous mutation of ACAN in a Korean family with proportionate short stature identified through targeted exome sequencing. We present a girl of 4 years and 9 months with a family history of short stature over three generations. The paternal grandmother is 143 cm tall (-3.8 as a Korean standard deviation score [SDS]), the father 155 cm (-3.4 SDS), and the index case 96.2 cm (-2.9 SDS). Evaluation for short stature showed normal growth hormone (GH) peaks in the GH provocation test and a mild delayed bone age for chronological age. This subject had clinical characteristics including a triangular face, flat nasal bridge, prognathia, blue sclerae, and brittle teeth. The targeted exome sequencing was applied to detect autosomal dominant growth palate disorder. The novel variant c.910G>A (p.Asp304Asn) in ACAN was identified and this variant was found in the subject's father using Sanger sequencing. This is the first case of Korean familial short stature due to ACAN mutation. ACAN should be considered for proportionate idiopathic short stature, especially in cases of familial short stature.