• Title/Summary/Keyword: Mutation analysis

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Optimization of Multiclass Support Vector Machine using Genetic Algorithm: Application to the Prediction of Corporate Credit Rating (유전자 알고리즘을 이용한 다분류 SVM의 최적화: 기업신용등급 예측에의 응용)

  • Ahn, Hyunchul
    • Information Systems Review
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    • v.16 no.3
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    • pp.161-177
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    • 2014
  • Corporate credit rating assessment consists of complicated processes in which various factors describing a company are taken into consideration. Such assessment is known to be very expensive since domain experts should be employed to assess the ratings. As a result, the data-driven corporate credit rating prediction using statistical and artificial intelligence (AI) techniques has received considerable attention from researchers and practitioners. In particular, statistical methods such as multiple discriminant analysis (MDA) and multinomial logistic regression analysis (MLOGIT), and AI methods including case-based reasoning (CBR), artificial neural network (ANN), and multiclass support vector machine (MSVM) have been applied to corporate credit rating.2) Among them, MSVM has recently become popular because of its robustness and high prediction accuracy. In this study, we propose a novel optimized MSVM model, and appy it to corporate credit rating prediction in order to enhance the accuracy. Our model, named 'GAMSVM (Genetic Algorithm-optimized Multiclass Support Vector Machine),' is designed to simultaneously optimize the kernel parameters and the feature subset selection. Prior studies like Lorena and de Carvalho (2008), and Chatterjee (2013) show that proper kernel parameters may improve the performance of MSVMs. Also, the results from the studies such as Shieh and Yang (2008) and Chatterjee (2013) imply that appropriate feature selection may lead to higher prediction accuracy. Based on these prior studies, we propose to apply GAMSVM to corporate credit rating prediction. As a tool for optimizing the kernel parameters and the feature subset selection, we suggest genetic algorithm (GA). GA is known as an efficient and effective search method that attempts to simulate the biological evolution phenomenon. By applying genetic operations such as selection, crossover, and mutation, it is designed to gradually improve the search results. Especially, mutation operator prevents GA from falling into the local optima, thus we can find the globally optimal or near-optimal solution using it. GA has popularly been applied to search optimal parameters or feature subset selections of AI techniques including MSVM. With these reasons, we also adopt GA as an optimization tool. To empirically validate the usefulness of GAMSVM, we applied it to a real-world case of credit rating in Korea. Our application is in bond rating, which is the most frequently studied area of credit rating for specific debt issues or other financial obligations. The experimental dataset was collected from a large credit rating company in South Korea. It contained 39 financial ratios of 1,295 companies in the manufacturing industry, and their credit ratings. Using various statistical methods including the one-way ANOVA and the stepwise MDA, we selected 14 financial ratios as the candidate independent variables. The dependent variable, i.e. credit rating, was labeled as four classes: 1(A1); 2(A2); 3(A3); 4(B and C). 80 percent of total data for each class was used for training, and remaining 20 percent was used for validation. And, to overcome small sample size, we applied five-fold cross validation to our dataset. In order to examine the competitiveness of the proposed model, we also experimented several comparative models including MDA, MLOGIT, CBR, ANN and MSVM. In case of MSVM, we adopted One-Against-One (OAO) and DAGSVM (Directed Acyclic Graph SVM) approaches because they are known to be the most accurate approaches among various MSVM approaches. GAMSVM was implemented using LIBSVM-an open-source software, and Evolver 5.5-a commercial software enables GA. Other comparative models were experimented using various statistical and AI packages such as SPSS for Windows, Neuroshell, and Microsoft Excel VBA (Visual Basic for Applications). Experimental results showed that the proposed model-GAMSVM-outperformed all the competitive models. In addition, the model was found to use less independent variables, but to show higher accuracy. In our experiments, five variables such as X7 (total debt), X9 (sales per employee), X13 (years after founded), X15 (accumulated earning to total asset), and X39 (the index related to the cash flows from operating activity) were found to be the most important factors in predicting the corporate credit ratings. However, the values of the finally selected kernel parameters were found to be almost same among the data subsets. To examine whether the predictive performance of GAMSVM was significantly greater than those of other models, we used the McNemar test. As a result, we found that GAMSVM was better than MDA, MLOGIT, CBR, and ANN at the 1% significance level, and better than OAO and DAGSVM at the 5% significance level.

Fragment Analysis for Detection of the FLT3-Internal Tandem Duplication: Comparison with Conventional PCR and Sanger Sequencing (FLT3-ITD 검출을 위한 절편분석법: 일반 중합효소연쇄반응 및 직접염기서열분석법과의 비교)

  • Lee, GunDong;Kim, Jeongeun;Lee, SangYoon;Jang, Woori;Park, Joonhong;Chae, Hyojin;Kim, Myungshin;Kim, Yonggoo
    • Laboratory Medicine Online
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    • v.7 no.1
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    • pp.13-19
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    • 2017
  • Background: We evaluated a sensitive and quantitative method utilizing fragment analysis of the fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD), simultaneously measuring mutant allele burden and length, and verified the analytical performance. Methods: The number and allelic burden of FLT3-ITD mutations was determined by fragment analysis. Serial mixtures of mutant and wild-type plasmid DNA were used to calculate the limit of detection of fragment analysis, conventional PCR, and Sanger sequencing. Specificity was evaluated using DNA samples derived from 50 normal donors. Results of fragment analysis were compared to those of conventional PCR, using 481 AML specimens. Results: Defined mixtures were consistently and accurately identified by fragment analysis at a 5% relative concentration of mutant to wild-type, and at 10% and 20% ratios by conventional PCR and direct sequencing, respectively. No false positivity was identified. Among 481 AML specimens, 40.1% (193/481) had FLT3-ITD mutations. The mutant allele burden (1.7-94.1%; median, 28.2%) and repeated length of the mutation (14-153 bp; median, 49 bp) were variable. The concordance rate between fragment analysis and conventional PCR was 97.7% (470/481). Fragment analysis was more sensitive than conventional PCR and detected 11 additional cases: seven had mutations below 10%, three cases represented conventional PCR failure, and one case showed false negativity because of short ITD length (14 bp). Conclusions: The new fragment analysis method proved to be sensitive and reliable for the detection and monitoring of FLT3-ITD in patients with AML. This could be used to simultaneously assess ITD mutant allele burden and length.

Digital painting: Image transfonnation, simulation, heterologie and transfonnation (현대회화에서의 형태와 물질 -Digital Transfiguration에 관한 연구-)

  • Jeong, Suk-Yeong
    • Journal of Science of Art and Design
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    • v.10
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    • pp.161-181
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    • 2006
  • The words which appeared in my theoretical study and work are image transformation to digital painting, simulation, heterologie and transfiguration, etc. Firstly, let's look into 'digital era' or 'new media era'. Nowadays, the image world including painting within the rapid social and cultural change, which is called as digital era, is having the dramatic change. Together with the development of scientific technology, large number of events which was deemed to be impossible is happening as real in image world Moreover, these changes in image world is greatly influencing to our life. The word which compresses this change of image world and shows is 'digital'. Digit, which means fingers in Latin, indicates separately changing signal, and to be more narrow, it indicates the continual signal of '0' and ' 1' in computer. The opposite word is 'analogue'. As analogue is the word meaning 'infer' or 'similarity', it indicates the signal or form which continuously changes along the series of time when it is compared to digital. Instead of analogue, digital is embossed as a major ruler along the whole area of our current culture. In whole culture and art area, and in whole generalscience, digital is appearing as it has the modernism and importance. The prefix, 'digital', e.g. digital media, digital culture, digital design, digital philosophy, etc, is treated as the synonym of modernism and something new. This advent of digital results the innovative change to the image world, creates the new beauty experience which we could not experience before, and forecasts the formation of advanced art and expansion of creative area. Various intellectual activities using computer is developing the whole world with making the infrastructure. Computer in painting work immediately accomplishes the idea of painters, takes part in simulation work, contingency such as abrupt reversal, extraction, twisting, shaking, obscureness, overlapping, etc, and timing to stimulate the creativity of painters, and provides digital formative language which enables new visual experience to the audience. When the change of digital era, the image appeared in my work is shown in 'transfiguration' like drawing. The word, 'transfiguration' does not indicate the completed and fixed real substance but indicate endlessly moving and floating shape. Thus, this concept is opposite to the substantial consideration, so that various concepts which is able to replace this in accordance with the similar cases are also exist such as change, deterioration, mutation, deformity of appearance and morphing which is frequently used in computer as a technical word. These concepts are not clearly classified, and variably and complicatedly related. Transfiguration basically means the denial of "objectivity' and '(continual) stagnation' or deviation from those. This phenomenon is appeared through the all art schools of art ever since the realism is denied in the 19th century. It is called as 'deformation' in case of expressionism, futurism, cubism, etc, in the beginning of the century, which its former indication is mostly preserved within the process of structural deviation and which has the realistic limit which should be preserved. On the contrary, dramatic transfiguration which has been showing in the modern era through surrealism is different in the point that dramatic transfiguration tends to show the deterioration and deviation rather than the preservation of indicated object. From this point, transfiguration coming out from morphing using computer deteriorates and hides the reality and furthermore, it replaces the 'reality'. Moreover, transfiguration is closely approached to the world of fake or 'imaginary' simulation world of Baudrillard. According to Baudrillard, the image hides and deteriorates the reality, and furthermore, expresses 'not existing' to 'imaginary' under the name of transfiguration. Certain reality, that is, image which is absent from the reality is created and overflowed, so that it finally replaces the reality. This is simulation as it is said by Baudrillard. In turn, Georges Bataille discusses about the image which is produced by digital technology in terms of heterologie. Image of heterologie is the visual signal which is established with the media. Image of media is to have the continuous characteristics of produce, extinction, and transformation, and its clear boundary between images becomes meaningless. The meaning of composition, excess, violation, etc of digital image is explained to heterological study or heteologie suggested as important meaning of Georges Bataille who is a heretic philosopher. As the form and image of mutation shows the shape in accordance with mechanical production, heterologie is introduced as very low materialism (or bas materialisme), in this theory. Heterologie as low materialism which is gradually changing is developing as a different concept and analysis because of the change of time in the late 20s century beside high or low meaning. Including my image, all images non-standardizes and transforms the code. However, reappearance and non-standardization of this code does not seem to be simple. The problem of transformation caused by transfiguration which appears in my digital drawing painting, simulation, heterologie, etc, are the continual problems. Moreover, the subject such as existence of human being, distance from the real life, politics and social problems are being extended to actual research and various expressing work. Especially, individual image world is established by digital painting transfiguration technique, and its change and review start to have the durability. The consciousness of observers who look at the image is changing the subject. Together with theoretical research, researchers are to establish the first step to approach to various image change of digital era painting through transfiguration technique using our realistic and historical image.

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Relationship of Resistance to Benzimidazole Fungicides with Mutation of β-Tubulin Gene in Venturia nashicola (Benzimidazole계 살균제에 대한 배 검은별무늬병균 Venturia nashicola 의 저항성과 β-Tubulin 유전자 돌연변이와의 관계)

  • Kwak, Yeonsoo;Min, Jiyoung;Song, Janghoon;Kim, Myeongsoo;Lee, Hanchan;Kim, Heung Tae
    • Research in Plant Disease
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    • v.23 no.2
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    • pp.150-158
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    • 2017
  • Pear scab caused by Venturia nashicola has been reported as an important disease of pear resulting in lowering the quality of pear fruits. In this study, it was conducted to investigate the relationship between resistance of V. nashicola and mutation of ${\beta}$-tubulin gene and the fungicide resistance in field isolate group in benzimidazole fungicides. Responce of V. nashicola to carbendazim could be classified into 3 groups as sensitive that does not grow at all on PDA amended with $0.16{\mu}g/ml$ of carbendazim, low resistance that could not grow in $4.0{\mu}g/ml$ medium, and high resistance that can grow even at $100{\mu}g/ml$. Thirty isolates of V. nashicola collected from 3 regions as Wonju, Naju, and Okcheon were highly resistant to carbendazim. Analysis of the nucleotide sequence of ${\beta}$-tubulin gene of V. nashicola showed that there was no difference in the nucleotide sequence between the sensitive and the low-resistant isolate, but GAG at codon 198 (glutamic acid) was replaced with GCG (alanine) in the high-resistant isolate. Among 10 isolates obtained from the Okcheon, 5 isolates showed the substitution of glycine for glutamic acid, which were resistant to carbendazim, but more sensitive to the mixture of carbendazim and diethofencarb than others. Through these results, all isolates of V. nashicola isolated in pear orchard were found to be resistant to benzimidazoles. Also, mutants E198A and E198G at ${\beta}$-tubulin were found to be important mechanisms of V. nashicola resistance against benzimidazole fungicides.

Studies on the Function of the Rv2435c Gene of the Mycobacterium bovis BCG (Mycobacterium bovis BCG Rv2435c 유전자의 기능에 대한 연구)

  • Lee Seung-Sil;Bae Young-Min
    • Journal of Life Science
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    • v.15 no.3 s.70
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    • pp.415-422
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    • 2005
  • library of the mutants was prepared by transposon mutagenesis of the Mycobacterium bovis BCG. We screened this library for the resistance to an anti-tuberculosis antibiotic, PA-824. Most of the mutants resistant to the PA-824 were not able to synthesize the coenzyme $F_{420}$ which is normally produced by the wild type M. bovis BCG strains. HPLC analysis of the cellular extract showed that one of those mutants which lost the ability to synthesize $F_{420}$ still produced F0. The insertion site of the transposon in this mutant was determined by an inverse PCR and the transposon was found to be inserted in the Rv2435c open reading frame (ORF). Rv2435c ORF is predicted to encode an 80.3 kDa protein. Rv2435c protein appears to be bound to the cytoplasmic membrane, its N-terminal present in the periplasm and C-terminal in the cytoplasm. The C-terminal portion of this protein is highly homologous with the adenylyl cyclases of both prokaryotes and eukaryotes. There are 15 ORFs which have homology with the class III AC proteins in the genome of the M. tuberculosis and M. bovis. Two of those, Rv1625c and Rv2435c, are highly homologous with the mammalian ACs. We cloned the cytoplasmic domain of the Rv2435c ORF and expressed it with six histidine residues attached on its C-terminal in Escherichia coli to find out if this protein is a genuine AC. Production of that protein in E. coli was proved by purifying the histidine-tagged protein by using the Ni-NTA resin. This protein, however, failed to complement the cya mutation in E. coli, indicating that this protein lacks the AC activity. All of the further attempts to convert this protein to a functional AC by a mutagenesis with UV or hydroxylamine, or construction of several different fusion proteins with Rv1625c failed. It is, therefore, possible that Rv2435c protein might affect the conversion of F0 to $F_{420}$ not by synthesizing cAMP but by some other way.

Relationship Between MC1R and ASIP Genotypes and Basic Coat Colors in Jeju Horses (제주마의 기본모색과 MC1R과 ASIP 유전자형 조합의 상관관계)

  • Kim, Nam-Young;Han, Sang-Hyun;Lee, Sung-Soo;Lee, Chong-Eon;Park, Nam-Geon;Ko, Moon-Suck;Yang, Young-Hoon
    • Journal of Animal Science and Technology
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    • v.53 no.2
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    • pp.107-111
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    • 2011
  • This study was undertaken to reveal the relationship between genetic variations and the basic coat color classification system in Jeju horses. Genetic variations of the melanocortinreceptor 1 (MC1R) and agouti signaling protein (ASIP) genes were investigated using pyrosequencing technique. A nucleotide substitution mutation for MC1R g.901C>T and an ASIP 11-bp deletion mutation were screened. Black horses had MC1R $E^+$/- ($E^+/E^+$ or $E^+/E^e$) and ASIP $A^a/A^a$ genotypes. In contrast, chestnut horse genotypes were MC1R $E^e/E^e$ and ASIP -/-. Thus, black and bay horses have at least one dominant MC1R allele, $E^+$, whereas chestnut horses have homozygous recessive alleles $E^e/E^e$. This suggests that the MC1R genotypes determine chestnut or black/bay coat color, regardless of the genotype distribution of ASIP. In addition, the horses with MC1R $E^+$/- and a dominant ASIP $A^A$/- allele showed bay coat color, but not black, suggesting that the ASIP $A^A$ allele represses black coat color development in the hairs of the body, but not in the mane and all four legs. Pedigree analysis showed a consistent relationship between the genotype distribution of the MC1R and ASIP genes and basic coat color patterns, even in the $F_1$ progeny. The results of this study revealed the relationship between the coat color phenotype and genetic background and suggested that useful information may be provided for molecular breeding of Jeju horses.

Diagnosis of Pigs Producing PSE Meat using DNA Analysis (DNA검사기법을 이용한 PSE 돈육 생산 돼지 진단)

  • Chung Eui-Ryong;Chung Ku-Young
    • Food Science of Animal Resources
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    • v.24 no.4
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    • pp.349-354
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    • 2004
  • Stress-susceptible pigs have been known as the porcine stress syndrome (PSS), swine PSS, also known as malignant hyperthermia (MH), is characterized as sudden death and production of poor meat quality such as PSE (pale, soft and exudative) meat after slaughtering. PSS and PSE meat cause major economic losses in the pig industry. A point mutation in the gene coding for the ryanodine receptor (RYR1) in porcine skeletal muscle, also known calcium (Ca$^{2+}$) release channel, has been associated with swine PSS and halothane sensitivity. We used the PCR-RFLP(restriction fragment length polymorphism) and PCR-SSCP (single strand conformation polymorphism) methods to detect the PSS gene mutation (C1843T) in the RYR1 gene and to estimate genotype frequencies of PSS gene in Korean pig breed populations. In PCR-RFLP and SSCP analyses, three genotypes of homozygous normal (N/M), heterozygous carrier (N/n) and homozygous recessive mutant (n/n) were detected using agarose or polyacrylamide gel electrophoresis, respectively. The proportions of normal, carrier and PSS pigs were 57.1, 35.7 and 7.1% for Landrace, 82.5, 15.8 and 1.7% far L. Yorkshire, 95.2, 4.8 and 0.0% for Duroc and 72.0, 22.7 and 5.3% for Crossbreed. Consequently, DNA-based diagnosis for the identification of stress-susceptible pigs of PSS and pigs producing PSE meat is a powerful technique. Especially, PCR-SSCP method may be useful as a rapid, sensitive and inexpensive test for the large-scale screening of PSS genotypes and pigs with PSE meat in the pork industry.y.

AGL gene mutation and clinical features in Korean patients with glycogen storage disease type III

  • Ko, Jung-Min;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of Genetic Medicine
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    • v.4 no.1
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    • pp.72-79
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    • 2007
  • Purpose : Glycogen storage disease type III (GSD-III) is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme, amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), is responsible for the debranching of the glycogen molecule during catabolism. The disease shows clinical and biochemical heterogeneity, reflecting genotype-phenotype heterogeneity among different patients. In this study, we aim at analyzing mutations of the AGL gene in three unrelated Korean GSD-III patients, and characterizing their clinical and laboratory findings. Methods : We characterized the clinical features of three unrelated Korean GSD-III patients by biochemical, histological and imaging studies. The 35 exons and part of exon-intron boundaries of AGL were analyzed by direct sequencing using genomic DNA extracted from the peripheral leukocytes of patients. Results : Diverse clinical features were observed in these patients including hepatomegaly (all patients), seizures (patient 2), grow th failure (patients 1 and 2), hyperlipidemia (patients 1 and 3), raised transaminase and creatine kinase concentrations (all patients), and mild cardiomyopathy (patient 2). Liver transplantation w as performed in patient 2 due to progressive hepatic fibrosis. A dministration of uncooked corn starch maintained normoglycemia and improved biochemical and growth profiles. 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 had c.1510_1511insT (p.Y 504L fsX 10), and patient 3 had c.3416 T >C (p.L 1139P) and c.1735+1 G>T (p.Y 538_R578delfsX 4) mutations. A part from the p.R428K mutation, the 4 other substitutions identified w ere nov el. Conclusion : GSD-III patients display variable phenotypic characteristics resembling those of GSD-Ia. Molecular defects in the AGL gene of Korean GSD-III patients are genetically heterogeneous.

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A Case of Progressive FSGS and Chronic Kidney Disease in Congenital Chloride Diarrhea with SLC26A3 Mutation (선천성 염소성 설사를 가진 환아에서 국소 분절 사구체경화증이 발생하여 만성 신장병으로 발전한 사례)

  • Seo, Young-Jun;Cheong, Han Bin;An, Seok Min;Sin, Woo Cheol;Bae, Eun Joo;Yoon, Jong Hyung;Jeong, Hwal Rim;Lee, Hong Jin
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.18 no.3
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    • pp.87-94
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    • 2018
  • We present the case of long-term observation of a patient with chronic kidney disease (CKD) caused by advanced focal segmental glomerulosclerosis (FSGS) resulting from underlying congenital chloride diarrhea (CLD). A 20-year-old woman was admitted for prolonged proteinuria despite conservative treatment for CLD. She was diagnosed with CLD and started taking KCl salt supplementation from the time of birth. Mild proteinuria was first found at 12 years of age, which progressed to moderate proteinuria at 16 years of age. At 16 years of age, CKD stage 2 with FSGS was diagnosed based on the initial assessment of the glomerular filtration rate (GFR) and kidney histology. On admission, we re-assessed her renal function, histology and genetic analysis. GFR had deteriorated to CKD stage 4 and renal histology revealed an advanced FSGS combined with tubulointerstitial fibrosis. A homozygous mutation in the SLC26A3 gene (c.2063-1G>T) was found by diagnostic exome sequencing and may have been inherited from both parents. CLD patients can be more vulnerable to renal injury, which may also cause progression of renal failure. Therefore, even if there is an early diagnosis and adequate salt supplementation, close monitoring of renal function and tailored treatment should be emphasized for renal protection and favorable CLD prognosis.

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A Case of Urologic Manifestation of IARS2-associated Leigh Syndrome (IARS2 유전자 연관 리 증후군(Leigh syndrome) 여아에서 방광기능장애 증례)

  • Hyunjoo Lee;Ji-Hoon Na;Young-Mock Lee
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.23 no.1
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    • pp.25-30
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    • 2023
  • Leigh syndrome is a rare progressive neurodegenerative mitochondrial disorder with clinical and genetic heterogeneity. Recently, balletic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes from Leigh and West syndrome to a rare syndrome CAGSSS characterized by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia syndrome (OMIM#616007). We describe a child with Korean Leigh syndrome with urologic manifestations resulting from a compound heterozygote mutation in IARS2. A 5-year-old girl visited the emergency room with a complaint of abdominal pain accompanied by abdominal distension. Abdominal-pelvic CT showed a markedly distended urinary bladder without definite obstructive lesions. She was diagnosed with neurogenic bladder dysfunction based on a urodynamic study. She had global delayed development due to neurologic regression after 6 months of age and a history of bilateral cataract surgery at the age of 2 years. Her brain magnetic resonance imaging showed symmetrically increased signal intensities in the bilateral putamen and caudate nuclei with diffuse cerebral atrophy. No gene variants were identified through whole-mitochondrial genome analysis. Whole exome sequencing was performed for diagnosis, and compound heterozygous pathogenic variants were identified in IARS2: c.2446C>T (p. Arg816Ter) and c.2450G>A (p. Arg817His). To the best of our knowledge, this is the first case report of bladder dysfunction manifestation in a patient with IARS2-related Leigh syndrome. Thus, it broadens the clinical and genetic spectrum of IARS2-associated diseases.

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