• Title/Summary/Keyword: Rare mutation

검색결과 212건 처리시간 0.026초

A case of Smith-Lemli-Opitz syndrome diagnosed by identification of mutations in the 7-dehydrocholesterol reductase (DHCR7) gene (7-dehydrocholesterol reductase (DHCR7) 변이로 진단된 Smith-Lemli-Opitz 증후군 1예)

  • Park, Mee Rim;Ko, Jung Min;Cheon, Chong-Keun;Kim, Gu-Hwan;Yoo, Han-Wook
    • Clinical and Experimental Pediatrics
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    • 제51권11호
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    • pp.1236-1240
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    • 2008
  • Smith-Lemli-Opitz syndrome (SLOS) is a rare, autosomal recessive disease caused by an inborn error in cholesterol synthesis. Patients with this disease suffer from multiple malformations due to reduced activity of 7-dehydrocholesterol reductase (DHCR7), which increases 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC) concentrations and decreases cholesterol concentration in body fluids and tissue. The SLOS phenotypic spectrum ranges from a mild disorder with behavioral and learning problems to a lethal disease characterized by multiple malformations. Here, we describe a newborn male with ambiguous genitalia who was diagnosed to have type II SLOS during the neonatal period. A clinical examination revealed low levels of unconjugated estriol in the maternal serum, and a variety of fetal ultrasound anomalies, including prenatal growth retardation. After birth, the infant was diagnosed to have congenital heart disease (Tetralogy of Fallot with severe pulmonary artery stenosis), cleft lip and palate, micrognathia, postaxial polydactyly, ambiguous genitalia, and cataracts. Clinical investigation revealed extremely low plasma cholesterol levels and the presence of mutation (homozygote of p.Arg352Gln) in the DHCR7 gene. The patient underwent palliative heart surgery (to widen the pulmonary artery) and received intravenous lipid supplementation. Cholesterol levels increased slightly, but not to normal values. The patient died from cardiopulmonary failure and sepsis 72 days after birth. This report provides the first description of a Korean patient with SLOS confirmed by verification of DHCR7 gene mutation and illustrates the need for early recognition and appropriate diagnosis of this disease.

AGL gene mutation and clinical features in Korean patients with glycogen storage disease type III (한국인 제3형 당원병 환자의 임상상 및 AGL 유전자형)

  • Ko, Jung Min;Lee, Jung Hyun;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of The Korean Society of Inherited Metabolic disease
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    • 제6권1호
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    • pp.15-23
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    • 2006
  • Purpose: Glycogen storage disease type III (GSD-III), is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme is amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), which is responsible for the debranching of the glycogen molecule during catabolism. The disease has been demonstrated to show clinical and biochemical heterogeneity, reflecting the genotype-phenotype heterogeneity among different patients. In this study, we analyzed mutations of the AGL gene in three unrelated Korean GSD-III patients and discussed their clinical and laboratory implications. Methods: We studied three GSD-III patients and the clinical features were characterized. Sequence analysis of 35exons and part exon-intron boundaries of the AGLgene in patients were carried out by direct DNA sequencing method using genomic DNA isolated from patients' peripheral leukocytes. Results: The clinical features included hepatomegaly (in all patients), seizures (in patient 2), growth failure (in patients 1), hyperlipidemia (in patients 1 and 3), raised transaminases and creatinine kinase concentrations (in all patients) and mild EKG abnormalities (in patients 2). Liver transplantation was performed in patient 2due to progressive hepatic fibrosis. Administration of raw-corn-starch could maintain normoglycemia and improve the condition. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 with c.1510_1511insT (p.Y504LfsX10), and patient 3 with c.3416 T>C (p.L1139P) and c.l735+1 G>T (Y538_R578delfsX4) mutations. Except R428K mutation, 4 other mutations identified in3 patients were novel. Conclusion: GSD-III patients have variable phenotypic characteristics resembling GSD-Ia. The molecular defects in the AGL gene of Korean GSD-III patients were genetically heterogeneous.

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A Case of Childhood Cerebral Form Adrenoleukodystrophy with Novel Mutation in the ABCD1 Gene (새로운 ABCD1 유전자의 돌연변이를 가지는 소아 대뇌형 부신백질이영양증 1례)

  • Shin, Young-Lim
    • Journal of The Korean Society of Inherited Metabolic disease
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    • 제12권1호
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    • pp.49-53
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    • 2012
  • X-linked adrenoleukodystrophy (ALD) is a rare inherited metabolic disease which results in impaired peroxisomal ${\beta}$-oxidation and the accumulation of very long chain fatty acids (VLCFA) in the adrenal cortex, the myelin of the central nervous system, and the testes. X-linked ALD is caused by mutations in the ABCD1 gene encoding an ATP-binding cassette transporter superfamily located in the peroxisomal membrane. This disease is characterized by a variety of phenotypes. The classic childhood cerebral ALD is a rapidly progressive demyelinating condition affecting the cerebral white matter before the age of 10 years in boys. We report the case of a 8-year-old with childhood cerebral X-linked ALD who developed inattention, hyperactivity, motor incoordination and hemiparesis. We diagnosed ALD with elevated plasma very long chain fatty acid level and diffuse high signal intensity lesions in both parieto-occipital white matter and cerebellar white matter in brain MRI. We identified a novel c.983delT (p.Met329CysfsX7) mutation of the ABCD1 gene. There is no correlation between X-ALD phenotype and mutations in the ABCD1 gene. Further studies for searching additional non-genetic factor which determine the phenotypic variation will be needed.

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Heterogenous Clinical Manifestations in Adult Patients with Late Diagnosis of Glycogen Storage Disease type Ia (성인기에 진단된 당원병 제 Ia형의 다양한 임상 양상)

  • Kim, Yoo-Mi;Cheon, Chong Kun;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of The Korean Society of Inherited Metabolic disease
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    • 제15권1호
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    • pp.9-17
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    • 2015
  • Glycogen storage disease (GSD) type Ia is rare inborn metabolic disorder, caused by glucose-6-phosphatase deficiency. It characterized by hepatomegaly, hypoglycemia, lactic acidosis, hypertriglyceridemia, and hyperuricemia and it is usually manifested in the infantile period. In addition, it is also associated with growth failure, pubertal delay, anemia, platelet dysfunction, osteopenia, and pulmonary hypertension. Hepatocellular adenoma and renal dysfunction are frequent late complications. Delayed diagnosis and inappropriate therapy lead to many complications such as growth failure, osteoporosis, refractory gout, renal failure, hepatocellular carcinoma (HCC), and pulmonary hypertension. Here, two Korean sisters diagnosed with GSD Ia, aged 33 and 36 respectively, were described and compared to recent articles about four adults with late diagnosis of GSD Ia. One sister had typical manifestations of GSD Ia including short stature (height, 145 cm), multiple hepatic adenoma, chronic kidney disease stage IV, and severe osteoporosis, whereas the older sister had normal stature (162 cm), one tiny hepatic nodule, and normal renal function. Direct sequencing of G6PC in two sisters identified a homozygous splicing mutation, c.645G>T, which is a prevalent mutation in Korea. Interestingly, our cases and four adults from recent reports had asymptomatic mild hypoglycemia and various manifestations including renal failure, HCC, fatty liver, or uncontrolled hyperlipidemia. These adult cases represent not only heterogenous phenotype to genotype within family members with GSD Ia but also long-term complications such as gouty arthritis, renal failure, and osteoporosis in untreated adult GSD Ia patients. In addition, lactic academia and hypertriglyceridemia are good markers of GSD Ia to distinguish from metabolic disease.

Mechanism of Resistance and Epithelial to Mesenchymal Transition of BRAF(V600E) Mutation Thyroid Anaplastic Cancer to BRAF(V600E) Inhibition Through Feedback Activation of EGFR (BRAF(V600E) 돌연변이 갑상선 역형성암에서 BRAF(V600E) 억제에 의한 EGFR 발현 증가가 표적치료에 대한 저항성발현과 상피-간질세포이행과정에 미치는 영향분석)

  • Byeon, Hyung Kwon;Na, Hwi Jung;Yang, Yeon Ju;Park, Jae Hong;Kwon, Hyeong Ju;Chang, Jae Won;Ban, Myung Jin;Kim, Won Shik;Shin, Dong Yeob;Lee, Eun Jig;Koh, Yoon Woo;Choi, Eun Chang
    • Korean Journal of Head & Neck Oncology
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    • 제30권2호
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    • pp.53-61
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    • 2014
  • Background and Objectives : Anaplastic thyroid carcinoma(ATC) is a rare but highly aggressive thyroid malignancy that is associated with an extremely poor survival despite the best multidisciplinary care. BRAF(V600E) mutation is detected in about a quarter of ATC, but unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response of ATC is reported to be low. The purpose of this study is to investigate the innate resistance mechanism responsible for this low treatment response to BRAF inhibitor and its effect on epithelial-mesenchymal transition(EMT). Materials and Methods : Two ATP cell lines, 8505C and FRO were selected and treated with PLX4032 and its drug sensitivity and effects on cell migration and EMT were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on both orthotopic and ectopic xenograft mouse models. Results : FRO cell line was more sensitive to PLX4032 treatment compared to 8505C cell line. The resistance to BRAF inhibition in 8505C was due to increased expression of EGFR. Effective inhibition of both EGFR and p-AKT was achieved after dual treatment with BRAF inhibitor(PLX4032) and EGFR inhibitor(Erlotinib). Similar results were confirmed on in vivo study. Conclusion : EGFR-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF(V600E) mutant ATC cells to PLX4032. Dual inhibition of BRAF and EGFR leads to sustained treatment response including cell invasiveness.

Glycogen Storage Disease Type III Confirmed by AGL Gene Analysis (AGL 유전자 검사로 확진된 제 3a형 당원병 1례)

  • Suh, Junghwan;Koo, Kyo Yeon;Kim, Kyu Yeun;Lee, Chul Ho;Yang, Jeong Yoon;Lee, Jin-Sung
    • Journal of The Korean Society of Inherited Metabolic disease
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    • 제12권2호
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    • pp.108-112
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    • 2012
  • Glycogen storage disease type III (GSD type III, OMIM #232400) is a rare autosomal recessive disease caused by a deficiency of the glycogen-debranching enzyme (GDE) with a mutation in the AGL gene (OMIM *610860). It is known to be bifunctional enzyme, that is, having two independent catalytic activities; 1,4-${\alpha}$-D-glucan 4-${\alpha}$-D-glycosyltransferase (EC 2.4.1.25) and amylo-1,6-glucosidase (EC 3.2.1.33) that occur at separate active sites on a single polypeptide chain. Most patients with GSD type III usually have symptoms related to decreased glycogenolysis in liver and muscles, such as hepatomegaly, hypoglycemia, failure to thrive, hyperlipidemia, muscle weakness and cardiomyopathy (type IIIa), however some patients show symptoms restricted to liver (type IIIb). GSD type III is diagnosed by enzyme test through liver or muscle biopsy or mutation analysis of the AGL gene. We report the case of GSD type III proven by gene study after liver biopsy, which revealed c.476delA, c.3444_3445insA in exon 6, 27 of AGL gene in Korean patient.

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X-linked Agammaglobulinemia Assiociated with Bronchiectasis : A Case Report (기관지 확장증을 동반한 X연관 무감마글로불린혈증 1예)

  • Yu, Chang-Min;Koh, Won-Jung;Kim, Kyung Chan;Lee, Byoung-Hoon;Hwang, Jung Hye;Kang, Eun Hae;Suh, Gee Young;Chung, Man Pyo;Kim, Hojoong;Kwon, O Jung;Ki, Chang-Seok;Kim, Jong-Won
    • Tuberculosis and Respiratory Diseases
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    • 제54권6호
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    • pp.628-634
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    • 2003
  • Bronchiectasis is defined as an abnormal, irreversible dilatation of the bronchi, which may result from a number of possible causes, and the recognition of these causes may lead to a specific management strategy. Immunodeficiency is known as one of the conditions associated with bronchiectasis. X-linked agammaglobulinemia is a rare inheritable immunodeficiency disorder, caused by a differentiation block, leading almost to the complete absence of B lymphocytes and plasma cells. The affected protein is a cytoplasmic protein tyrosine kinase, Bruton's tyrosine kinase. The early detection and treatment with immunoglobulin replacement are most important for the management of recurrent infections and for reducing severe complications. We report a 20-year-old male patient, with X-linked agammaglobulinemia associated with bilateral bronchiectasis, carrying a missense mutation(R520P) in the BTK gene.

A Case of Autosomal Recessive Pseudohypoaldosteronism Type 1 with a Novel Mutation in the SCNN1A Gene (SCNN1A 유전자 변이로 발생한 상염색체 열성 가성 저 알도스테론증 1형 1례)

  • Kim, Su-Yon;Lee, Joo Hoon;Cheong, Hae Il;Park, Young Seo
    • Childhood Kidney Diseases
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    • 제17권2호
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    • pp.137-142
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    • 2013
  • Pseudohypoaldosteronism (PHA) is a condition characterized by renal salt wasting, hyperkalemia, and metabolic acidosis due to renal tubular resistance to aldosterone. Systemic PHA1 is a more severe condition caused by defective transepithelial sodium transport due to mutations in the genes encoding the ${\alpha}$ (SCNN1A), ${\beta}$ (SCNN1B), or ${\gamma}$ (SCNN1G) subunits of the epithelial sodium channel at the collecting duct, and involves the sweat glands, salivary glands, colon, and lung. Although systemic PHA1 is a rare disease, we believe that genetic studies should be performed in patients with normal renal function but with high plasma renin and aldosterone levels, without a history of potassium-sparing diuretic use or obstructive uropathy. In the present report, we describe a case of autosomal recessive PHA1 that was genetically diagnosed in a newborn after severe hyperkalemia was noted.

Utilizing cell-free DNA to validate targeted disruption of MYO7A in rhesus macaque pre-implantation embryos

  • Junghyun Ryu;Fernanda C. Burch;Emily Mishler;Martha Neuringer;Jon D. Hennebold;Carol Hanna
    • Journal of Animal Reproduction and Biotechnology
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    • 제37권4호
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    • pp.292-297
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    • 2022
  • Direct injection of CRISPR/Cas9 into zygotes enables the production of genetically modified nonhuman primates (NHPs) essential for modeling specific human diseases, such as Usher syndrome, and for developing novel therapeutic strategies. Usher syndrome is a rare genetic disease that causes loss of hearing, retinal degeneration, and problems with balance, and is attributed to a mutation in MYO7A, a gene that encodes an uncommon myosin motor protein expressed in the inner ear and retinal photoreceptors. To produce an Usher syndrome type 1B (USH1B) rhesus macaque model, we disrupted the MYO7A gene in developing zygotes. Identification of appropriately edited MYO7A embryos for knockout embryo transfer requires sequence analysis of material recovered from a trophectoderm (TE) cell biopsy. However, the TE biopsy procedure is labor intensive and could adversely impact embryo development. Recent studies have reported using cell-free DNA (cfDNA) from embryo culture media to detect aneuploid embryos in human in vitro fertilization (IVF) clinics. The cfDNA is released from the embryo during cell division or cell death, suggesting that cfDNA may be a viable resource for sequence analysis. Moreover, cfDNA collection is not invasive to the embryo and does not require special tools or expertise. We hypothesized that selection of appropriate edited embryos could be performed by analyzing cfDNA for MYO7A editing in embryo culture medium, and that this method would be advantageous for the subsequent generation of genetically modified NHPs. The purpose of this experiment is to determine whether cfDNA can be used to identify the target gene mutation of CRISPR/Cas9 injected embryos. In this study, we were able to obtain and utilize cfDNA to confirm the mutagenesis of MYO7A, but the method will require further optimization to obtain better accuracy before it can replace the TE biopsy approach.

Diffuse Leptomeningeal Glioneuronal Tumor with FGFR1 Mutation in a 29-Year-Old Male (29세 남성에서 발생한 FGFR1 돌연변이를 동반한 미만성 연수막성 신경교종)

  • Minsu Kim;Ki Rim Lee;Gheeyoung Choe;Kihwan Hwang;Jae Hyoung Kim
    • Journal of the Korean Society of Radiology
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    • 제84권4호
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    • pp.970-976
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    • 2023
  • This study reports on diffuse leptomeningeal glioneuronal tumor (DL-GNT) in a 29- year-old male. DL-GNT is a rare central nervous system (CNS) tumor mostly seen in children and only few cases have been reported in adult patients. Our patient presented with a chronic headache that lasted for five months. MR imaging showed mild hydrocephalus, multiple rim-enhancing nodular lesions in the suprasellar cistern, diffuse leptomeningeal enhancement in the lumbosacral area, and multiple small non-enhancing cyst-appearing lesions not suppressed on fluid attenuated inversion recovery (FLAIR) images in the bilateral basal ganglia, thalami, and cerebral hemispheres. Under the impression of germ cell tumor with leptomeningeal seeding, the patient underwent trans-sphenoidal tumor removal. DL-GNT was pathologically confirmed and FGFR1 mutation was detected through a next-generation sequencing test. In conclusion, a combination of leptomeningeal enhancement and multiple parenchymal non-enhancing cyst-appearing lesions not suppressed on FLAIR images may be helpful for differential diagnosis despite overlapping imaging features with many other CNS diseases that have leptomeningeal enhancement.