• Journal of Genetic Medicine
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• 제15권1호
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• pp.28-33
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• 2018

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the deficiency of ${\alpha}$-galactosidase A. Patients with classical FD present acroparesthesia, hypohidrosis, cornea verticillata, disseminated angiokeratoma, and microalbuminuria in childhood, and develop life-threatening renal, cardiac, and cerebrovascular complications typically after the fourth decade of life. To date, more than 700 mutations responsible for FD have been identified in the human GLA gene. Herein, we report a novel GLA mutation, c.1117_1141del25 (p.Gly373Profs*10), identified in an 11-year-old Korean boy with FD presenting early cardiac and neurologic manifestation and in other affected family members. The boy had acroparesthesia, hypohidrosis, cornea verticillata, and left ventricular hypertrophy. His mother and sister also had acroparesthesia. Two males on the mother's side had similar pain and died of unknown causes. The plasma ${\alpha}$-galactosidase A activity (4.1 nmol/hr/mg protein) of the patient was markedly lower than the mean value of the controls. The plasma level of globotriaosylsphingosine was elevated in the patient and all the carriers. We concluded the novel GLA mutation c.1117_1141del25 is a pathogenic mutation for FD, probably related to the early cardiac manifestation of FD.

• Preventive Nutrition and Food Science
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• 제9권3호
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• pp.276-282
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• 2004

Marginal Zn deficiency is prevalent through the world and yet human zinc status has not been properly assessed due to the lack of a reliable diagnostic indicator. One potential possibility for zinc status assessment using Zn-binding protein, metallothionein (MT)-mRNA, has been proposed. The purpose of the present study was aimed to show whether measurement of mononuclear cell (MNC) MT mRNA, using a competitive-reverse transcriptase-polymerase chain reaction (competitive-RT-PCR) assay, could indicate zinc status in human subjects. In this study, MNC MT-mRNA expression was measured using a competitive-RT-PCR to compare before and after 14 days of zinc supplementation (50 mg Zn/das zinc gluconate). RT-PCR oligonucleotide primers which were designed to amplify both a 278 bp segment of the human MT-2A cDNA and a 198 bp mutant competitor cDNA template from MNCs, were prepared. MT-2A mRNA was normalized by reference to the housekeeping gene, $\beta$-actin, mRNA for which was also measured by competitive-RT-PCR. There was considerable inter-individual variation in MT-mRNA concentration and yet, the mean MT-2A mRNA level increased 4.7-fold after Zn supplementation, as compared to before Zn supplementation. This MT-2A mRNA level was shown as the same pattern and, even more sensitive assay, compared to the conventional plasma and red blood cells (RBCs) Zn assessment in which plasma and RBCs zinc levels increased 2.3- and 1.2-fold, respectively (p<0.05). We suggest that MT competitive-RT-PCR can be a useful assessment tool for evaluating human zinc status.

• 대한유전성대사질환학회지
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• 제22권2호
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• pp.58-62
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• 2022

폼페병(PD, Pompe disease), 2형 당원축적병(Glycogen storage disease type II)은 보통염색체 열성 질환으로 용해소체 효소인 acid maltase (acid α-glucosidase, GAA) 결핍으로 인한 대사근육병이다. 한 종류의 효소 결핍에 의한 질환이지만, GAA의 결핍정도와 유전자형에 따라 임상양상이 다르게 나타난다. 발병 시기에 따라 크게 영아형 폼페병(infantile onset Pompe disease, IOPD), 성인형 폼페병(late onset Pompe disease, LOPD)으로 나눌 수 있다. 저자들은 신생아기 때 호흡곤란증후군을 진단받고 치료받은 후 잠시 혈중 CK 증가가 확인되었으나 다른 임상증상 없이 경과 관찰 후 호전되었고, LSD 스크리닝 검사 결과 상 GAA 수치가 0.58 umol/h/L로 감소되어 있음을 확인한 1례에 대해 보고하고자 한다. 해당 환아를 PD 의증으로 고려하여 시행한 GAA enzyme essay 상 total GAA level은 16.2 nmol/2hr/mg protein, GAA with acarbose level은 2.0 nmol/2hr/mg protein, acarbose/total level의 비율은 12.0%로 낮은 수치를 확인하였다. 환아의 유전자 검사 상 exon #4에서 두개의 likely pathogenic heterozygous mutation인 c.752C>T (p.Ser251Leu), c.761C>T (p.Ser254Leu), exon #12에서 heterozygous mutation인 c.1726G>A (p.Gly576Ser), exon #15에서 heterozygous mutation인 c.2065G>A (p.Glu689 Lys)이 확인되었다. 환아의 7세 오빠는 유전자 검사에서 정상으로 확인되었고, 아버지는 환아에서 동일하게 확인된 exon #12에서 heterozygous mutation인 c.1726G>A(p.Gly576Ser), exon #15에서 heterozygous mutation인 c.2065G>A (p.Glu689Lys)이, 어머니에서는 exon #4에서 두 개의 likely pathogenic heterozygous mutation인 c.752C>T (p.Ser251Leu), c.761C>T (p.Ser254Leu)가 확인되었다. Pathogenic한 유전자 두개가 있으면 보통 환자로 인식될 수 있으나 이 환아에서처럼 pathogenic한 유전자 두 개가 있더라도 cis 형태로 하나처럼 움직인 경우 PD 환자가 아니라 carrier 일 수 있다는 것을 경험한 증례였다. 이에 PD 환아의 유전검사 결과를 해석할 시 pathogenic variant 유전자가 두 개일지라도 혹시 cis 형태로 하나의 유전자인지를 확인하여, pseudodeficiency나 potential LOPD carrier일 수 있는 점을 고려하며 여러 임상 양상을 취합하여 진료를 시행하는 것이 필요하다.

• 한국식품영양과학회지
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• 제15권4호
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• pp.72-80
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• 1986

The purpose of this study was to investigate the dietary-intake and that of health by mean of questionarie and interview for male and female old persons living in Seoul area. The contents of study included general aspects, physical status and health, nutrient intake, and food intake frequency. The results from the above survey are summarized as follows ; 1. The age group in the range of 60 to 79 years old was 71%, and the average number of family was 4.9. The educational level was 56% of elderly persons were elementary or middle school graduates . 42.8% of elderly persons had an average monthly income of \490,000 to 300,000. 2. The aged average height, weight, and physical index were 164.9cm, 55.8kg and 20.4 in male, 152.7cm, 46.0kg and 20.3 in female which were lower than the Korean average standard. (male; 167.0cm, 61.0kg, female; 156.0cm, 55.0kg) In the degree of health self-consciousness, percentage distribution of poor and very poor was 29% in male, 59% in female. Among the condition of disease, neuralgia was 23.8%, hypertension was 17.2%, diabetes was 5.4%. 3. Average daily calorie intake was $63.9{\sim}70.4%$ for male and $76.4{\sim}83.9%$ for female which were lower than the Recommended Dietary Allowances for Koreans. Protein intake was $42.9{\sim}57.3g$ (which was $72.8{\sim}82.6%$ RDA) for elderly person, the proportion of animal protein to total protein intake were $24.3{\sim}28.2%$($12.9{\sim}16.2g$). Iron, Vitamin $B_1$, $B_2$ Niacin intake exceeded the RDA, but the intake of Calcium, Vitamin C were far less than that of RDA. 4. In the correlations between nutritional intakes and environmental factors and health, economic living situations and educational level as the factors which might influence the condition of nutritional intake was significant(P<0.01). 5. Food intake frequency of meats, fishes, eggs, for average of $1{\sim}2$ days per week were $44.8{\sim}50.5%$, that of milk and milk products for scarecely week were 42.9.% Correlation of food intake frequency was divided three levels-good, fair, poor. Food intake frequency as the factors which might influence the condition of nutritional intake was significant(P<0.01). The results of the survey reveal that many of elderly show evidence of general nutrient intake deficiency, it requires first of all importance of nutrition to improve nutritional level through to promotion of elderly health.

• Journal of Nutrition and Health
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• 제35권9호
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• pp.943-951
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• 2002

This study was designed to investigate the effects of iron supplementation and nutrition education on the iron status and anemia of high school girls. The subjects resided in Ulsan city in Korea and were already diagnosed as having anemia or iron deficiency. Over a period of three months, one iron tablet (80 mg Fe as ferrous sulfate/day) was administered to the iron deficient subjects and two tablets (160 mg Fe as ferrous sulfate/day) were administered to the anemia subjects. The average height and weight of anemia subjects were 161.24 $\pm$ 4.50 cm and 50.87 $\pm$ 5.86 kg, respectively. The average BMI (kg/$m^2$ )was 19.58 $\pm$ 2.03 and the PIBW(percent ideal body weight) were 92.52 $\pm$ 9.84%. Except for vitamin A and vitamin C intakes, the intake levels of all other nutrients were below the RDA. Total calorie intakes of anemia subjects were 73.5% of RDA. The iron intakes of subjects from food were 69. 1% of RDA and the Ca intakes were 59.1% of RDA. The basal hemoglobin(Hb) concentration of anemia subjects averaged 10.77 $\pm$ 1.33 g/dl, and this increased significantly (p < 0.001) to 12.12 $\pm$ 1.08 g/dl, after iron supplementation. The basal ferritin, and transferrin saturations ｛TS (%)｝of anemia subjects were 12.51 $\pm$ 15.19 ng/$m\ell$ and 8.43 $\pm$ 7.56%, respectively, and these significantly increased to 20.59 $\pm$ 22.39 ng/$m\ell$ and 15.56 $\pm$ 12.87%, respectively. The level of total iron binding protein (TIBC) significantly decreased from the initial 486.80 $\pm$ 70.16 $\mu\textrm{g}$/dl to 417.86 $\pm$ 67.73 $\mu\textrm{g}$/dl (p < 0.001) after iron supplementation. For the iron deficiency subjects, the ferritin, iron and TS(%) levels were increased significantly (p < 0.001) and the TIBC levels were significantly (p <0.001) decreased after iron supplementation. Anemia symptoms such as 'Feeling blue (p<0.05)', 'Decreased ability to concentrate (p<0.001)' and 'Poor memory (p<0.05)' improved significantly after iron supplementation in the anemia subjects. The number of tablets administered was positively correlated with changes in serum hemoglobin (t=0.194, p< 0.01), serum ferritin (t=0.181, p<0.01), TS(%) (t=0.141, p<0.05), and hematocrit (t=0.254, p<0.01), and was negatively correlated with changes in TIBC (t=-0.143. p<0.05) and red cell distribution width (RDW, t=-0.140, p<0.05). In conclusion, daily iron supplementation was effective in improving the iron status and reducing symptoms of anemia in high school girls. (Korean J Nutrition 35 (9) : 943~951,2002)

• Clinical and Experimental Pediatrics
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• 제55권2호
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• pp.48-53
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• 2012

Purpose: Gaucher disease is caused by a ${\beta}$-glucocerebrosidase (GBA) deficiency. The aim of this study is to investigate the clinical and genetic characteristics according to subtypes of Gaucher disease in the Korean population. Methods: Clinical findings at diagnosis, $GBA$ mutations, and clinical courses were reviewed in 20 patients diagnosed with Gaucher disease. Results: Eleven patients were diagnosed with non-neuronopathic type, 2 with acute neuronopathic type, and 7 with chronic neuronopathic type. Most patients presented with hepatosplenomegaly, thrombocytopenia, and short stature. In the neuronopathic group, variable neurological features, such as seizure, tremor, gaze palsy, and hypotonia, were noted at age $8.7{\pm}4.3$ years. B cell lymphoma, protein-losing enteropathy, and hydrops fetalis were the atypical manifestations. Biomarkers, including chitotriosidase, acid phosphatase, and angiotensin-converting enzyme, increased at the initial evaluation and subsequently decreased with enzyme replacement treatment (ERT). The clinical findings, including hepatosplenomegaly, thrombocytopenia, and skeletal findings, improved following ERT, except for the neurological manifestations. L444P was the most common mutation in our cohort. One novel mutation, R277C, was found. Conclusion: Although the clinical outcome for Gaucher disease improved remarkably following ERT, the outcome differed according to subtype. Considering the high proportion of the neuronopathic form in the Korean population, new therapeutic strategies targeting the central nervous system are needed, with the development of a new scoring system and biomarkers representing clinical courses in a more comprehensive manner.

• 생명과학회지
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• 제20권9호
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• pp.1420-1425
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• 2010

선천성 면역이란 감염성 질환에 대응하는 분자들의 네트워크가 반응하는 숙주의 첫 번째 방어 메카니즘이다. 간에서 만들어져 혈액에 존재하는 Mannose-binding lectin (MBL)은 선천성 면역에 관여하는 단백질군인 collectin에 속하는 분자로서 감염성 질병을 유발하는 다양한 세균, 바이러스, 효모, 곰팡이 및 원생동물의 표면에 존재하는 특징적인 당쇄를 인식한다. 이런 감염성 인자들의 표면에 드러난 당쇄의 공통적인 패턴을 MBL이 인식하여 자기(self)와 비자기(non-self)를 구분하기 때문에 MBL을 패턴 인식 분자(pattern recognition molecule)라고 한다. MBL은 MBL2 유전자에 의해 만들어지며, MBL2 유전형은 여러 가지 다형성(polymorphisms)이 있는 것으로 나타났다. MBL2 유전자의 변이는 상당히 많은 사람에서 나타나며, MBL 결여의 원인이다. MBL 결여는 감염성 질환에 대한 감수성을 증가시키므로, MBL의 유전적 변이와 임상적 중요성에 대해 많은 연구가 진행 되어져 왔다. 이 총설은 현재 우리가 알고 있는 MBL의 구조와 기능에 대해 전반적으로 논의하고자 한다.

• Nutrition Research and Practice
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• 제10권6호
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• pp.623-628
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• 2016

BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype. MATERIALS/METHODS: Male C57BL/6 mice were fed a regular diet (RD), high-fat diet (HFD), or HFD supplemented with quercetin (HF+Que, 0.5g/kg diet) for nine weeks. Inflammatory cytokines and macrophage markers were measured by ELISA and RT-PCR, respectively. HO-1 protein was measured by Western blotting. RESULTS: Quercetin supplementation decreased levels of inflammatory cytokines ($TNF{\alpha}$, IL-6) and increased that of the anti-inflammatory cytokine (IL-10) in the livers of HFD-fed mice. This was accompanied by upregulation of M2 macrophage marker genes (Arg-1, Mrc1) and downregulation of M1 macrophage marker genes ($TNF{\alpha}$, NOS2). In co-cultures of lipid-laden hepatocytes and macrophages, treatment with quercetin induced HO-1 in the macrophages, markedly suppressed expression of M1 macrophage marker genes, and reduced release of MCP-1. Moreover, these effects of quercetin were blunted by an HO-1 inhibitor and deficiency of nuclear factor E2-related factor 2 (Nrf2) in macrophages. CONCLUSIONS: Quercetin reduces obesity-induced hepatic inflammation by promoting macrophage phenotype switching. The beneficial effect of quercetin is associated with Nrf2-mediated HO-1 induction. Quercetin may be a useful dietary factor for protecting against obesity-induced steatohepatitis.

• Molecules and Cells
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• 제38권11호
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• pp.925-935
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• 2015

DNA methylation is a well-characterized epigenetic modification that plays central roles in mammalian development, genomic imprinting, X-chromosome inactivation and silencing of retrotransposon elements. Aberrant DNA methylation pattern is a characteristic feature of cancers and associated with abnormal expression of oncogenes, tumor suppressor genes or repair genes. Ten-eleven-translocation (TET) proteins are recently characterized dioxygenases that catalyze progressive oxidation of 5-methylcytosine to produce 5-hydroxymethylcytosine and further oxidized derivatives. These oxidized methylcytosines not only potentiate DNA demethylation but also behave as independent epigenetic modifications per se. The expression or activity of TET proteins and DNA hydroxymethylation are highly dysregulated in a wide range of cancers including hematologic and non-hematologic malignancies, and accumulating evidence points TET proteins as a novel tumor suppressor in cancers. Here we review DNA demethylation-dependent and -independent functions of TET proteins. We also describe diverse TET loss-of-function mutations that are recurrently found in myeloid and lymphoid malignancies and their potential roles in hematopoietic transformation. We discuss consequences of the deficiency of individual Tet genes and potential compensation between different Tet members in mice. Possible mechanisms underlying facilitated oncogenic transformation of TET-deficient hematopoietic cells are also described. Lastly, we address non-mutational mechanisms that lead to suppression or inactivation of TET proteins in cancers. Strategies to restore normal 5mC oxidation status in cancers by targeting TET proteins may provide new avenues to expedite the development of promising anti-cancer agents.

• Nutrition Research and Practice
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• 제17권1호
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• pp.135-148
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• 2023

BACKGROUND/OBJECTIVES: In times of disaster, simplified and minimized nutritional standards are necessary for a quick response to provide nutritious relief food. This study aimed to develop nutrient-based nutritional standards for foodservice at shelters during disasters in the Republic of Korea (South Korea). SUBJECTS/METHODS: The standards were developed in 2 phases. First, nutrients to be included in the standards were selected. Initial candidates were selected considering 3 aspects: preceding standards, insufficient intake during disasters, and inadequate intake among South Koreans. Final selection was made by excluding nutrients for 3 reasons: nutrients for which there is no deficiency concern in South Korea, nutrients whose intake data were not available, or nutrients whose values presented by Dietary Reference Intakes for Koreans are difficult to achieve based on the current diet among South Koreans. Second, the reference values of energy and the selected nutrients were calculated. The reference values for the entire population who were 1-year-old and over were calculated by multiplying the estimated energy requirements or the recommended nutrient intake and the proportion of each age and sex group. Respective reference values were also calculated for 4 different age groups (1-5, 6-11, 12-64, and ≥ 65-year-old). RESULTS: The standards for the entire population were 2,000 kcal for energy, 55 g for protein, 650 ㎍ retinol activity equivalents for vitamin A, 95 mg for vitamin C, 1.1 mg for thiamin, 1.3 mg for riboflavin, 14 mg niacin equivalents for niacin, 350 ㎍ dietary folate equivalents for folic acid, 750 mg for calcium, and 11 mg for iron. Four additional standards corresponding to each age group were developed. CONCLUSIONS: The nutritional standards during disasters were developed for South Korea, including energy and 9 nutrients with reference values for the entire population and 4 different age groups. The standards will contribute to maintaining the health of disaster evacuees in South Korea.