• Annals of Pediatric Endocrinology and Metabolism
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• 제23권4호
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• pp.235-239
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• 2018

Most cases of congenital hyperthyroidism are autoimmune forms caused by maternal thyroid stimulating antibodies. Nonautoimmune forms of congenital hyperthyroidism caused by activating mutations of the thyrotropin receptor (TSHR) gene are rare. A woman gave birth to a boy during an emergency cesarean section at 33 weeks of gestation due to fetal tachycardia. On the 24th day of life, thyroid function tests were performed due to persistent tachycardia, and hyperthyroidism was confirmed. Auto-antibodies to TSHR, thyroid peroxidase, and thyroglobulin were not found. The patient was treated with propylthiouracil and propranolol, but hyperthyroidism was not well controlled. At 3 months of age, the patient had craniosynostosis and hydrocephalus, and underwent a ventriculoperitoneal shunt operation. Direct sequencing of the TSHR gene showed a heterozygous mutation of c.1899C>A (p.Asp633Glu) in exon 10. No mutations were discovered in any of the parents in a familial genetic study. We have reported a case of sporadic nonautoimmune congenital hyperthyroidism, by a missense mutation of the TSHR gene, for the first time in South Korea.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.109-109
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• 2003

Even though success in birth of live offspring from nuclear transfer(NT) using somatic cells in many species, detailed information on processes or mechanisms of development are not well known. Cytoplasm of bovine oocyte has been known to support the development of nuclear transferred embryos using nuclear donor cells from different species. Therefore, interspecies NT might be used to find answers of some questions in basic aspect of nuclear transfer In this study, we examined the developmental potential of reconstructed embryos when bovine oocyte as a cytoplasm recipient and mouse embryonic fibroblast as a nuclear donor were used. The nuclear transfer units were aliocated in Group 1 (murine block media and normal media) and Group 2. (bovine block media and normal media). NT units were not blocked at 2-cell stage regardless of types of medium. On mouse media, poor development of interspecies NT units was observed compared to bovine media. However, as NT units cultured in bovine normal medium, embryos developed over 8-cell stage. Further studies performed to increase the developmental rate in condition of antioxidant treatment. Despite low development, bovine-murine interspecies nuclear transferred embryos could develop to blastocysts and they showed that blastocyts rate of antioxidant group was superior to those of non-antioxidant group. Next, we investigated gene expression pattern which is carried out for zygotic activation. The Xist gene is expressed in female mouse embryo after zygotic activation of 4-cell stage. But interspecies nuclear transferred embryos do not express Xist gene at 4-cell stage. As a result, it is suggested that the bovine cytoplasm controls the early preimplantation development in interspecies NT However, the development of later stages might require genomic control from transferred donor nucleus. Therefore, even though the involvement of several other factors such as mitochondrial incompatibility, effective development of embryos produced by interspecies NT requires proper genomic activation of donor nucleus after overcoming the cytoplasmic control of recipient oocytes.

• Asian-Australasian Journal of Animal Sciences
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• 제31권5호
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• pp.686-695
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• 2018

Objective: The objective of this study was to investigate the effects of dietary choline supplementation on hepatic lipid metabolism and gene expression in finishing pigs with intrauterine growth retardation (IUGR). Methods: Using a $2{\times}2$ factorial design, eight normal birth weight (NBW) and eight IUGR weaned pigs were fed either a basal diet (NBW pigs fed a basal diet, NC; IUGR pigs fed a basal diet, IC) or a diet supplemented with two times more choline than the basal diet (NBW pigs fed a high-choline diet, NH; IUGR pigs fed a high-choline diet, IH) until 200 d of age. Results: The results showed that the IUGR pigs had reduced body weight compared with the NBW pigs (p<0.05 from birth to d 120; p = 0.07 from d 120 to 200). Increased (p<0.05) free fatty acid (FFA) and triglyceride levels were observed in the IUGR pigs compared with the NBW pigs. Choline supplementation decreased (p<0.05) the levels of FFAs and triglycerides in the serum of the pigs. The activities of malate dehydrogenase and glucose 6-phosphate dehydrogenase were both increased (p<0.05) in the livers of the IUGR pigs. Choline supplementation decreased (p<0.05) malate dehydrogenase activity in the liver of the pigs. Gene expression of fatty acid synthase (FAS) was higher (p<0.05) in the IC group than in the other groups, and choline supplementation decreased (p<0.05) FAS and acetyl-CoA carboxylase ${\alpha}$ expression in the livers of the IUGR pigs. The expression of carnitine palmitoyl transferase 1A (CPT1A) was lower (p<0.05) in the IC group than in the other groups, and choline supplementation increased (p<0.05) the expression of CPT1A in the liver of the IUGR pigs and decreased (p<0.01) the expression of hormone-sensitive lipase in both types of pigs. The gene expression of phosphatidylethanolamine N-methyltransferase (PEMT) was higher (p<0.05) in the IC group than in the other groups, and choline supplementation significantly reduced (p<0.05) PEMT expression in the liver of the IUGR pigs. Conclusion: In conclusion, the lipid metabolism was abnormal in IUGR pigs, but the IUGR pigs consuming twice the normal level of choline had improved circulating lipid parameters, which could be related to the decreased activity of nicotinamide adenine dinucleotide phosphate-generating enzymes or the altered expressions of lipid metabolism-related genes.

• Clinical and Experimental Pediatrics
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• 제51권11호
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• pp.1236-1240
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• 2008

Smith-Lemli-Opitz 증후군은 콜레스테롤 합성 과정의 장애로 발생하는 상염색체 열성으로 유전되는 드문 질환으로 다양한 기형을 동반한다. 이는 DHCR7 유전자 변이로 인한 활성도 저하로 발생하는 질환으로 7DHC, 8DHC의 증가 및 체내 콜레스테롤의 감소에 따른 임상상을 특징으로 한다. 저자들은 국내에서 최초로 SLO 증후군을 유전자 분석을 통하여 진단하였기에 이를 문헌 고찰과 함께 보고하는 바이다.

• 한국환경보건학회지
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• 제35권5호
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• pp.343-354
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• 2009

Since Barker found associations between low birth weight and several chronic diseases later in life, the hypothesis of fetal origins of adult disease (aka, Barker Hypothesis) and epigenetics have been emerging as a new paradigm for geneenvironment interaction of chronic disease. Epigenetics is the study of heritable changes in gene silencing that occur without any change in DNA sequence. Gene expression can be regulated by several epigenetic mechanisms, including DNA methylation and histone modifications, which may be associated with chronic conditions, such as cancers, cardiovascular disease, and type-2 diabetes. One carbon metabolism which involves the transfer of a methyl group catalyzed by DNA methyltransferase is an important mechanism by which DNA methylation occurs in promoter regions and/or repetitive elements of the genome. Environmental factors may induce epigenetic modification through production of reactive oxygen species, alteration of methyltransferase activity, and/or interference with methyl donors. In this review, we introduce recent studies of epigenetic modification and environmental factors, such as heavy metals, environmental hormones, air pollution, diet and psychosocial stress. We also discuss epigenetic perspectives of early life environmental exposure and late life disease occurrence.

• 한국가축번식학회지
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• 제27권4호
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• pp.333-338
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• 2003

Transgenic mice containing GH Receptor (GHR) gene fused to metallothionein promoter were analyzed to evaluate effect of GHR expression on growth in vivo. Three founder mice lines contained copies of GHR transgene and transmitted these genes into F$_1$ and F$_2$ progenies. The mRNA expression of transgene was identified using RT-PCR with GHR genes in tissues. To analyze the effects of transgenes on growth performance, body weights of pups were measured at 4, 10 and 14 weeks after birth. The body weight of transgenic mice was higher compared with that of non-transgenic control mice regardless of sex (P<0.05). Body weights between transgenic and non-transgenic mice were increased with aging. Overall, GHR transgenic mice tended to grow about 10 to 15 ％ faster than non-transgenic mice without any pathological defects.

• Molecules and Cells
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• 제38권3호
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• pp.251-258
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• 2015

Germline mutations in the breast cancer type 2 susceptibility gene (BRCA2) are linked to familial breast cancer and the progressive bone marrow failure syndrome Fanconi anaemia. Established Brca2 mouse knockout models show embryonic lethality, but those with a truncating mutation at the C-terminus survive to birth and develop thymic lymphoma at an early age. To overcome early lethality and investigate the function of BRCA2, we used T cell-specific conditional Brca2 knockout mice, which were previously shown to develop thymic lymphoma at a low penetrance. In the current study we showed that the number of peripheral T cells, particularly na$\ddot{i}$ve pools, drastically declined with age. This decline was primarily ascribed to improper peripheral maintenance. Furthermore, heterozygous mice with one wild-type Brca2 allele manifested reduced T cell numbers, suggesting that Brca2 haploinsufficiency might also result in T cell loss. Our study reveals molecular events occurring in Brca2-deficient T cells and suggests that both heterozygous and homozygous Brca2 mutation may lead to dysfunction in T cell populations.

• Journal of Genetic Medicine
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• 제10권2호
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• pp.94-98
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• 2013

Dystrophinopathy, caused by mutations in the DMD gene, presents with variable clinical phenotypes ranging from the severe Duchenne muscular dystrophy (DMD) to the milder Becker muscular dystrophy(BMD) forms. DMD is a recessive X-linked form of muscular dystrophy. Two-thirds of mothers of affected males are thought to be DMD carriers. Approximately 2.5-7.8% of female DMD carriers have muscle weakness and are categorized as manifesting DMD carriers. The symptoms of female carriers of DMD range from mild muscle weakness to severe gait problems. The most commonly presented symptom is mild proximal muscle weakness, which is often asymmetric and progressive, but shows variable clinical spectrum with BMD of more severe DMD-like phenotype. Atypical presentations in manifesting carriers are myalgia or cramps without limb weakness, isolated cardiomyopathy and camptocormia. Multiplex PCR and MLPA analysis are common techniques to identify mutations in the DMD gene. Relationship between X-chromosome inactivation and clinical severity is not clear. Female carriers of DMD are not less common, and they have an important role of birth of a male DMD.

• Asian-Australasian Journal of Animal Sciences
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• 제15권2호
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• pp.179-183
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• 2002

The fragment in intron I of FSH-${\beta}$ gene was amplified by PCR. According to the polymorphism, we analyzed the distribution of FSH-${\beta}$ retroposon in different pig breeds; its inheritance pattern in Large White${\times}$Meishan reference family; and the association of FSH-${\beta}$ retroposon with litter size, female reproductive organs measurement, ultrasonic backfat and other traits. The results showed that almost each Chinese indigenous pig had the retroposon, while foreign pig breeds rarely had; the frequencies of porcine FSH-${\beta}$ retroposon were strongly associated with breeds (p<0.01); the pattern of inheritance was consistent with Mendelian fashion; total number born (TNB) and number born alive (NBA) were increased per FSH-${\beta}$ retroposon (p<0.01) with additive effects of 1.2-1.8 and 1.4-1.8 pigs/litter, respectively; between the FSH-${\beta}$ retroposon carriers and non-carriers, there was an insignificant difference in the measurement of female reproductive organs, body weight at birth, backfat thickness, loin meat height, lean meat percentage, teat number, days to 100 kg, and average daily gain.

• 대한유전성대사질환학회지
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• 제17권3호
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• pp.103-108
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• 2017

가부키 증후군(Kabuki syndrome)은 특징적인 얼굴(아치형의 넓은 눈썹, 낮은 코끝, 큰 귓바퀴, 아래 외측 안검 외전), 골격계 이상, 출생 후 성장 지연, 그리고 경도의 정신 지체를 특징으로 나타내는 선천성 이상 질환이다. 또한, 선천성 심장기형, 비뇨생식기 기형, 구개구순열을 포함한 위장관 기형, 안검 하수 등의 증상이 동반되기도 한다. 감염과 면역질환, 경련, 내분비 문제, 청력 손실이 나타날 수 있다. 가부키 증후군의 대부분은 12번 염색체의 장완에 위치한 KMT2D 유전자의 돌연변이에 의해 발병된다. KMT2D 유전자의 돌연변이로 생성된 비정상적인 KMT2D 단백질로 인해 신체의 여러 장기와 조직의 특정 유전자의 활성이 정상적으로 이뤄지지 못하여, 결과적으로 가부키 증후군의 특징적인 외형과 기능장애가 나타난다. 출생시 선천성 심장 기형, 갑상선 기능 저하 및 일과성 저혈당 과거력이 있던 환아가 만 4세경 성장 지연, 아치형 눈썹, 낮은 코끝, 아래 외측 안검 외전, 큰 귓바퀴 등의 얼굴 생김새를 보여 시행한 분자유전학적 검사에서 KMT2D의 exon 15에서 새로운 frameshift mutation이 발견되어 증례를 보고하는 바이다. 가부키 증후군은 성장 지연 뿐 아니라, 발달 장애 및 행동 장애, 사춘기 여아의 경우 조기 가슴 발육을 포함한 내분비적 문제, 사시, 안검하수 등의 안과적 문제, 만성 중이염, 청력 손실, 감염, 경련 등 다양한 증상을 나타낼 수 있기 때문에 조기에 질환을 진단하고, 임상증상에 따라 적절한 중재를 할 수 있도록, 정기적으로 신장, 몸무게, 머리둘레, 발달상태, 청각과 시각상태를 확인하는 것이 중요하다. 따라서 여러 장기의 선천 기형을 보이는 환아의 경우, 임상의는 출생 당시에는 두드러지지 않을 수 있는 특징적인 얼굴 생김새, 성장 지연, 정신 지체 등의 이상에 대해 유의하여야 한다. 분자유전학적 검사는 임상적으로 가부키 증후군이 의심되는 환아를 조기에 진단할 수 유용한 방법이며, 앞으로도 가부키 증후군과 연관된 유전자 변이에 대한 연구가 더욱 필요할 것으로 사료된다.