Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.614
Filtrar
1.
Blood Research ; : 17-26, 2020.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-820807

RESUMO

BACKGROUND: DNMT3A mutations occur in approximately 20% of AML cases and are associated with changes in DNA methylation. CDKN2B plays an important role in the regulation of hematopoietic progenitor cells and DNMT3A mutation is associated with CDKN2B promoter methylation. We analyzed the characteristics of DNMT3A mutations including their clinical significance in AML and their influence on promoter methylation and CDKN2B expression.METHODS: A total of 142 adults, recently diagnosed with de novo AML, were enrolled in the study. Mutations in DNMT3A, CEBPA, and NPM1 were analyzed by bidirectional Sanger sequencing. We evaluated CDKN2B promoter methylation and expression using pyrosequencing and RT-qPCR.RESULTS: We identified DNMT3A mutations in 19.7% (N=28) of enrolled patients with AML, which increased to 29.5% when analysis was restricted to cytogenetically normal-AML. Mutations were located on exons from 8–23, and the majority, including R882, were found to be present on exon 23. We also identified a novel frameshift mutation, c.1590delC, in AML with biallelic mutation of CEBPA. There was no significant difference in CDKN2B promoter methylation according to the presence or type of DNMT3A mutations. CDKN2B expression inversely correlated with CDKN2B promoter methylation and was significantly higher in AML with R882H mutation in DNMT3A. We demonstrated that DNMT3A mutation was associated with poor AML outcomes, especially in cytogenetically normal-AML. The DNMT3A mutation remained as the independent unfavorable prognostic factor after multivariate analysis.CONCLUSION: We characterized DNMT3A mutations in AML and revealed the association between the DNMT3A mutation and CDKN2B expression and clinical outcome.


Assuntos
Adulto , Metilação de DNA , Éxons , Mutação da Fase de Leitura , Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda , Metilação , Análise Multivariada
2.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-816628

RESUMO

Since parathyroid hormone (PTH) was first isolated and its gene (PTH) was sequenced, only eight PTH mutations have been discovered. The C18R mutation in PTH, discovered in 1990, was the first to be reported. This autosomal dominant mutation induces endoplasmic reticulum stress and subsequent apoptosis in parathyroid cells. The next mutation, which was reported in 1992, is associated with exon skipping. The substitution of G with C in the first nucleotide of the second intron results in the exclusion of the second exon; since this exon includes the initiation codon, translation initiation is prevented. An S23P mutation and an S23X mutation at the same residue were reported in 1999 and 2012, respectively. Both mutations resulted in hypoparathyroidism. In 2008, a somatic R83X mutation was detected in a parathyroid adenoma tissue sample collected from a patient with hyperparathyroidism. In 2013, a heterozygous p.Met1_Asp6del mutation was incidentally discovered in a case-control study. Two years later, the R56C mutation was reported; this is the only reported hypoparathyroidism-causing mutation in the mature bioactive part of PTH. In 2017, another heterozygous mutation, M14K, was detected. The discovery of these eight mutations in the PTH gene has provided insights into its function and broadened our understanding of the molecular mechanisms underlying mutation progression. Further attempts to detect other such mutations will help elucidate the functions of PTH in a more sophisticated manner.


Assuntos
Apoptose , Estudos de Casos e Controles , Códon de Iniciação , Estresse do Retículo Endoplasmático , Éxons , Humanos , Hiperparatireoidismo , Hipoparatireoidismo , Íntrons , Doenças das Paratireoides , Glândulas Paratireoides , Hormônio Paratireóideo , Neoplasias das Paratireoides
3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781305

RESUMO

OBJECTIVE@#To detect pathogenic variant of ARSA gene in an infant with late infantile metachromatic leukodystrophy (MLD).@*METHODS@#The male proband had an onset of walking dysfunction and seizure at 28 months. Arylsulfatase A activity of his peripheral blood leucocytes was 26.9 nmol/mg.17h, and cranial MRI showed wild symmetrical demyelination. With genomic DNA extracted from his peripheral blood sample, all coding exons and splicing sites of the ARSA gene were subjected to Sanger sequencing. PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. Ucsf chimera software was used to analyze the impact of candidate variants on the secondary structure of the protein product. Impact of potential variants was also analyzed with software including PolyPhen-2, Mutation Taster, SIFT and PROVEAN. Whole-exome sequencing was carried out to identify additional variants which may explain the patient's condition.@*RESULTS@#The proband was found to harbor compound heterozygous variants of the ARSA gene [c.467G>A (p.Gly156Asp) and c.960G>A (p.Trp320*)], neither of which was reported previously. As predicted by Ucsf chimera software, the c.960G>A (p.Trp320*) variant may demolish important secondary structures including α-helix, β-strand and coil of the ARSA protein, causing serious damage to its structure and loss of function. The c.467G>A (p.Gly156Asp) variant was predicted to be "probably damaging" by PolyPhen-2, Mutation Taster and SIFT software.@*CONCLUSION@#The patient's condition may be attributed to the compound heterozygous c.467G>A (p.Gly156Asp) and c.960G>A (p.Trp320*) variants of the ARSA gene. Above results have facilitated genetic counseling and prenatal diagnosis for this family.


Assuntos
Cerebrosídeo Sulfatase , Genética , Éxons , Genética , Feminino , Humanos , Lactente , Leucodistrofia Metacromática , Genética , Masculino , Mutação , Genética , Gravidez , Processamento de RNA , Genética
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781301

RESUMO

OBJECTIVE@#To explore the genetic basis of an infant featuring congenital cataract, developmental delay and proteinuria.@*METHODS@#Clinical data and peripheral blood samples of the family were collected. Potential variants were screened by using targeted capture and high-throughput sequencing on a NextSeq 500 platform. Suspected variant was verified by quantitative PCR. Pathogenicity of the candidate variant was predicted based on clinical presentation and laboratory tests.@*RESULTS@#The infant's phenotypes included brain development retardation and proteinuria. Cranial MRI indicated widening of cerebral fissure, bilateral frontal and temporal subarachnoid cavities, and dysplasia of white matter myelination in posterior angular of ventricle. A novel duplication of exons 5 to 16 of the OCRL gene was found in the patient. His mother has carried the same duplication variant.@*CONCLUSION@#The duplication variant of the OCRL gene probably underlies the oculo-cerebro-renal syndrome in the infant. Due to the heterogeneity of its clinical manifestation, pertinent genetic detection is essential for acurrate diagnosis of patients who have the related phenotypes.


Assuntos
Éxons , Genética , Testes Genéticos , Humanos , Lactente , Síndrome Oculocerebrorrenal , Genética , Fenótipo , Monoéster Fosfórico Hidrolases , Genética
5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781290

RESUMO

OBJECTIVE@#To explore the molecular basis for an individual with ABO subtype.@*METHODS@#The ABO phenotype of the proband was determined by convention serological testing. Exons 6 and 7 of the ABO gene were subjected to PCR amplification and bi-directional Sanger sequencing. Haplotypes for exons 6 and 7 of the proband was determined using an ABO haplotype-specific amplification and sequencing technique.@*RESULTS@#Red blood cells of the proband showed a 4+ agglutination strength with anti-A or anti-H, no agglutination reaction with anti-A1, and a 3+ agglutination strength with anti-B. His serum had no reaction with standard A cells, O cells or self cells, but was weakly reactive with B cells at 4℃. The proband was assigned as an ABO subtype based on his serological features. Bi-directional sequencing of the ABO gene revealed heterozygosity of 261 G/del, 297AG, 526CG, 657CT, 703GA, 803GC and 930GA, and homozygosity of 796CC in the proband. Haplotype-specific amplification and sequencing showed that one of his alleles was ABO*O.01.01, and another contained a c.796A>C variation compared with the ABO*B.01 allele, which led to replacement of methionine by leucine at position 266. Searching the ABO allele database of International Society of Blood Transfusion suggested the variation to be a novel one.@*CONCLUSION@#The c.796A>C variation in the ABO*B.01 allele probably underlies the CisAB subtype. Accurate identification of the ABO subtype requires combined use of serological method and genetic testing.


Assuntos
Sistema ABO de Grupos Sanguíneos , Genética , Alelos , Éxons , Variação Genética , Genótipo , Humanos , Masculino , Fenótipo , Análise de Sequência de DNA
6.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-759593

RESUMO

BACKGROUND: The recent expansion of knowledge about various ABO alleles has led to the need for a comprehensive measure to cover the numerous polymorphisms dispersed in the ABO gene. A few studies have examined the diversity of the O allele compared to A or B subgroup alleles, resulting in antigenic changes. This study investigated the relationship between the serologic and molecular genetic characteristics of the O alleles in the Korean population. METHODS: One hundred and five samples from healthy blood group O subjects were selected randomly. The isoagglutinin titer was measured using a tube agglutination and gel microcolumn assay. The ABO alleles were analyzed by sequencing exons 6 and 7 of the ABO gene. When the origin of a heterozygous nucleotide sequence was ambiguous, it was separated into a single allele using mono-allele amplification or cloning. RESULTS: The median IgM isoagglutinin titer was eight. In contrast, the median IgG anti-A and anti-B isoagglutinin titers were 64 and 32, respectively. The IgG isoagglutinin titer showed a significant increase with age (P<0.0001). Six O alleles were observed in 105 blood group O populations by sequencing. The O01 and O02 alleles were common (0.57, 0.36). Three rare O alleles (O04, O05, and O06) and one novel non-deletional O allele were found. CONCLUSION: The distribution of isoagglutinin titers of blood group O and the genetic frequency of O alleles in this study would form the basis of the development and interpretation of ABO genotyping and serologic workup in the Korean population.


Assuntos
Aglutinação , Alelos , Sequência de Bases , Células Clonais , Clonagem de Organismos , Éxons , Imunoglobulina G , Imunoglobulina M , Biologia Molecular , Análise de Sequência
7.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-759578

RESUMO

RHD genotyping is a useful adjunct to serologic testing. Although the use of RHD genotyping in the detection of Asia type DEL in serological D negative Koreans is gradually increasing, it is rarely requested for patients with a known weak D phenotype. This paper reports the first Korean case of a 52-year-old female patient with serologic weak D phenotype and weak D type 33 (c.520G>A at exon 4 of RHD) identified by RHD exon 1 to 10 sequencing. In silico analysis predicted that the RHD c.520G>A (V174M) results in a serologic weak D phenotype.


Assuntos
Ásia , Simulação por Computador , Éxons , Feminino , Humanos , Coreia (Geográfico) , Pessoa de Meia-Idade , Fenótipo , Testes Sorológicos
8.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-758887

RESUMO

Canine MDR1 gene mutations produce translated P-glycoprotein, an active drug efflux transporter, resulting in dysfunction or over-expression. The 4-base deletion at exon 4 of MDR1 at nucleotide position 230 (nt230[del4]) in exon 4 makes P-glycoprotein lose function, leading to drug accumulation and toxicity. The G allele of the c.-6-180T>G variation in intron 1 of MDR1 (single nucleotide polymorphism [SNP] 180) causes P-glycoprotein over-expression, making epileptic dogs resistant to phenobarbital treatment. Both of these mutations are reported to be common in collies. This study develops a more efficient method to detect these two mutations simultaneously, and clarifies the genotype association with the side effects of chemotherapy. Genotype distribution in Taiwan was also investigated. An oligonucleotide microarray was successfully developed for the detection of both genotypes and was applied to clinical samples. No 4-base deletion mutant allele was detected in dogs in Taiwan. However, the G allele variation of SNP 180 was spread across all dog breeds, not only in collies. The chemotherapy adverse effect percentages of the SNP 180 T/T, T/G, and G/G genotypes were 16.7%, 6.3%, and 0%, respectively. This study describes an efficient way for MDR1 gene mutation detection, clarifying genotype distribution, and the association with chemotherapy.


Assuntos
Alelos , Animais , Cães , Tratamento Farmacológico , Éxons , Genótipo , Íntrons , Métodos , Análise de Sequência com Séries de Oligonucleotídeos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Fenobarbital , Taiwan
9.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763821

RESUMO

Identification of fusion gene is of prominent importance in cancer research field because of their potential as carcinogenic drivers. RNA sequencing (RNA-Seq) data have been the most useful source for identification of fusion transcripts. Although a number of algorithms have been developed thus far, most programs produce too many false-positives, thus making experimental confirmation almost impossible. We still lack a reliable program that achieves high precision with reasonable recall rate. Here, we present FusionScan, a highly optimized tool for predicting fusion transcripts from RNA-Seq data. We specifically search for split reads composed of intact exons at the fusion boundaries. Using 269 known fusion cases as the reference, we have implemented various mapping and filtering strategies to remove false-positives without discarding genuine fusions. In the performance test using three cell line datasets with validated fusion cases (NCI-H660, K562, and MCF-7), FusionScan outperformed other existing programs by a considerable margin, achieving the precision and recall rates of 60% and 79%, respectively. Simulation test also demonstrated that FusionScan recovered most of true positives without producing an overwhelming number of false-positives regardless of sequencing depth and read length. The computation time was comparable to other leading tools. We also provide several curative means to help users investigate the details of fusion candidates easily. We believe that FusionScan would be a reliable, efficient and convenient program for detecting fusion transcripts that meet the requirements in the clinical and experimental community. FusionScan is freely available at http://fusionscan.ewha.ac.kr/.


Assuntos
Linhagem Celular , Conjunto de Dados , Éxons , Fusão Gênica , Análise de Sequência de RNA , Translocação Genética
10.
Experimental Neurobiology ; : 485-494, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763779

RESUMO

Vacuolar protein sorting-associated protein 13B (VPS13B), also known as COH1, is one of the VPS13 family members which is involved in transmembrane transport, Golgi integrity, and neuritogenesis. Mutations in the VPS13B gene are associated with Cohen syndrome and other cognitive disorders such as intellectual disabilities and autism spectrum disorder (ASD). However, the patho-physiology of VPS13B-associated cognitive deficits is unclear, in part, due to the lack of animal models. Here, we generated a Vps13b exon 2 deletion mutant mouse and analyzed the behavioral phenotypes. We found that Vps13b mutant mice showed reduced activity in open field test and significantly shorter latency to fall in the rotarod test, suggesting that the mutants have motor deficits. In addition, we found that Vps13b mutant mice showed deficits in spatial learning in the hidden platform version of the Morris water maze. The Vps13b mutant mice were normal in other behaviors such as anxiety-like behaviors, working memory and social behaviors. Our results suggest that Vps13b mutant mice may recapitulate key clinical symptoms in Cohen syndrome such as intellectual disability and hypotonia. Vps13b mutant mice may serve as a useful model to investigate the pathophysiology of VPS13B-associated disorders.


Assuntos
Animais , Transtorno do Espectro Autista , Transtornos Cognitivos , Éxons , Humanos , Deficiência Intelectual , Memória de Curto Prazo , Camundongos , Modelos Animais , Hipotonia Muscular , Fenótipo , Teste de Desempenho do Rota-Rod , Comportamento Social , Aprendizagem Espacial , Água
11.
Chonnam Medical Journal ; : 99-103, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763277

RESUMO

Breast cancer is the second most common cancer in Korean women. Germline mutations in the BRCA1 and BRCA2 genes cause hereditary breast cancer and are detected in 15–20% of hereditary breast cancer. We investigated the BRCA1 and BRCA2 mutations in 114 familial breast cancer patients using next-generation sequencing. We confirmed 20 different mutations of BRCA1 and BRCA2 in 25 subjects (21.9%). Two such mutations in eight patients were novel (not reported in any variant database or previous study). Six mutations have been reported as disease-causing mutations in public databases. Seven mutations were found only in a single nucleotide polymorphism database and one mutation has been reported in Korea. The BRCA1/2 mutation frequency was similar to that of other studies on familial breast cancer patients in the Korean population. Further studies should examine more cases and mutations of whole exons.


Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Mama , Éxons , Feminino , Genes BRCA2 , Mutação em Linhagem Germinativa , Humanos , Coreia (Geográfico) , Taxa de Mutação , Polimorfismo de Nucleotídeo Único
12.
Cancer Research and Treatment ; : 1518-1526, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763209

RESUMO

PURPOSE: The purpose of this study was to investigate the prognostic significance of liver kinase b1 (LKB1) loss in patients with operable colon cancer (CC). MATERIALS AND METHODS: Two hundred sixty-two specimens from consecutive patients with stage III or high-risk stage II CC, who underwent surgical resection with curative intent and received adjuvant chemotherapy with fluoropyrimidine and oxaliplatin, were analyzed for LKB1 protein expression loss, by immunohistochemistry as well as for KRAS exon 2 and BRAF(V600E) mutations by Sanger sequencing and TS, ERCC1, MYC, and NEDD9 mRNA expression by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: LKB1 expression loss was observed in 117 patients (44.7%) patients and correlated with right-sided located primaries (p=0.032), and pericolic lymph nodes involvement (p=0.003), BRAF(V600E) mutations (p=0.024), and TS mRNA expression (p=0.041). Patients with LKB1 expression loss experienced significantly lower disease-free survival (DFS) (hazard ratio [HR], 1.287; 95% confidence interval [CI], 1.093 to 1.654; p=0.021) and overall survival (OS) (HR, 1.541; 95% CI, 1.197 to 1.932; p=0.002), compared to patients with LKB1 expressing expressing tumors. Multivariate analysis revealed LKB1 expression loss as independent prognostic factor for both decreased DFS (HR, 1.217; 95% CI, 1.074 to 1.812; p=0.034) and decreased OS (HR, 1.467; 95% CI, 1.226 to 2.122; p=0.019). CONCLUSION: Loss of tumoral LKB1 protein expression, constitutes an adverse prognostic factor in patients with operable CC.


Assuntos
Quimioterapia Adjuvante , Colo , Neoplasias do Colo , Intervalo Livre de Doença , Éxons , Humanos , Imuno-Histoquímica , Fígado , Linfonodos , Análise Multivariada , Fosfotransferases , Reação em Cadeia da Polimerase , Prognóstico , Recidiva , Transcrição Reversa , RNA Mensageiro
13.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763144

RESUMO

PURPOSE: We tried to evaluate whether there are any specific features in treatment outcomes of firstline afatinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), compared with gefitinib or erlotinib. MATERIALS AND METHODS: We analyzed patients treated with first-line afatinib, gefitinib, or erlotinib for advanced EGFR-mutant NSCLC at Samsung Medical Center between 2014 and 2016. RESULTS: In total, 467 patients received first-line afatinib (n=165), gefitinib (n=230), or erlotinib (n=72). Afatinib was used more often in patients with tumors harboring deletion in exon 19 (Del19), whereas the gefitinib group had more elderly, females, and never smokers. The median progression-free survival (PFS) time for afatinib, gefitinib, and erlotinib was 19.1 months, 13.7 months, and 14.0 months, respectively (p=0.001). The superior PFS of afatinib was more remarkable in subgroups of Del19 or uncommon EGFR mutations. Overall toxicity profiles of the three drugs were comparable, though more grade 3 or 4 toxicities were detected in afatinib (7.3%) compared with gefitinib (2.6%) or erlotinib (1.8%). The common grade 3 or 4 toxicities of afatinib included diarrhea (3.0%), paronychia (2.4%), and skin rash (1.8%). Dose modification was more frequently required in patients treated with afatinib (112/165, 68%), compared with gefitinib (5/230, 2%) and erlotinib (4/72, 6%). Interestingly, however, dose reduction in the afatinib group did not impair its efficacy in terms of PFS (dose reduction vs. no reduction group, 23.5 months vs. 12.4 months). CONCLUSION: First-line afatinib showed satisfactory efficacy data and manageable toxicity profiles.


Assuntos
Idoso , Carcinoma Pulmonar de Células não Pequenas , Diarreia , Intervalo Livre de Doença , Cloridrato de Erlotinib , Exantema , Éxons , Feminino , Humanos , Paroniquia , Receptores ErbB
14.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763132

RESUMO

PURPOSE: Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for approximately 4% of all EGFR mutations. Given the rarity of this mutation, its clinical outcomes are not fully established. MATERIALS AND METHODS: Between 2009 and 2017, non-small cell lung cancer (NSCLC) patients who showed an exon 20 insertion were retrospectively reviewed for clinical characteristics and outcomes, including responses to chemotherapy (CTx) or targeted therapy. RESULTS: Of 3,539 NSCLC patients who harbored an activating EGFR mutation, 56 (1.6%) had an exon 20 insertion. Of the advanced NSCLC patients, 27 of 1,479 (1.8%) had an exon 20 insertion. The median overall survival was 29.4 months (95% confidence interval 9.3 to 49.6) for 27 advancedNSCLC patients. The 22 patientswho received systemic CTx achieved a 50.0% response rate and a 77.2% disease control rate, with 4.2 months of progression-free survival. Six patients received EGFR tyrosine kinase inhibitors (TKIs). Three of the four patients that had only an exon 20 insertion showed progressive disease, while one showed stable disease. The othertwo patients had an exon 20 insertion and another EGFR mutation and achieved a partial response. CONCLUSION: The incidence of an exon 20 insertion mutation is rare in Korea and occasionally accompanied by other common EGFR mutations. Although the response to systemic CTx. in these patients is comparable to that of patients with other mutations, the response rate to first- or second-generation EGFR TKIs is quite low. Therefore, the development of a more efficient agent is urgently needed.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Intervalo Livre de Doença , Tratamento Farmacológico , Éxons , Humanos , Incidência , Coreia (Geográfico) , Mutagênese Insercional , Proteínas Tirosina Quinases , Receptores ErbB , Estudos Retrospectivos
15.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763103

RESUMO

BACKGROUND: The aim of this study was to compare epidermal growth factor receptor (EGFR) mutations between non-small cell lung cancer (NSCLC) and corresponding brain metastases (BMs) in Korea society. METHODS: From 2011 to 2016, a total of 74 patients underwent surgical resection of a metastatic brain tumor from NSCLC. Among them, we performed retrospective analysis for 46 patients who underwent EGFR sequencing of primary NSCLC tissues. RESULTS: Among these 46 cases, 18 (39.1%) cases showed EGFR mutation in primary lung cancer. Detected mutation sites were exon 19 (8 cases), exon 21 (6 cases), exon 18 (1 cases), and multiple mutations (3 cases). In 18 cases of BM, EGFR mutation studies were done. Among them, 8 (25.6%) cases showed mutation on exon 19 (5 cases) or exon 21 (3 cases). To compare EGFR mutation status between primary lung cancer and BM, 18 paired tissues from both NSCLC and matched BM were collected. Four (22.5%) patients were discordant for the status of EGFR between primary and metastatic sites. CONCLUSION: EGFR mutations were significantly discordant between primary tumors and corresponding metastases in a significant portion of NSCLC. In treatment of BM of EGFR mutant metastatic NSCLC, due to possibility of discordance, pathologic confirming through brain biopsy is recommended.


Assuntos
Biópsia , Neoplasias Encefálicas , Encéfalo , Carcinoma Pulmonar de Células não Pequenas , Fator de Crescimento Epidérmico , Éxons , Humanos , Coreia (Geográfico) , Neoplasias Pulmonares , Metástase Neoplásica , Receptores ErbB , Estudos Retrospectivos
16.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762621

RESUMO

Vanishing white matter (VWM) disease is an autosomal recessive disorder that affects the central nervous system of a patient, and is caused by the development of pathogenic mutations in any of the EIF2B1-5 genes. Any dysfunction of the EIF2B1-5 gene encoded eIF2B causes stress-provoked episodic rapid neurological deterioration in the patient, followed by a chronic progressive disease course. We present the case of a patient with an infantile-onset VWM with the pre-described specific clinical course, subsequent neurological aggravation induced by each viral infection, and the noted consequent progression into a comatose state. Although the initial brain magnetic resonance imaging did not reveal specific pathognomonic signs of VWM to distinguish it from other types of demyelinating leukodystrophy, the next-generation sequencing studies identified heterozygous missense variants in EIF2B3, including a novel variant in exon 7 (C706G), as well as a 0.008% frequency reported variant in exon 2 (T89C). Hence, the characteristic of unbiased genomic sequencing can clinically affect patient care and decisionmaking, especially in terms of the consideration of genetic disorders such as leukoencephalopathy in pediatric patients.


Assuntos
Encéfalo , Sistema Nervoso Central , Coma , Fator de Iniciação 2B em Eucariotos , Exoma , Éxons , Humanos , Leucoencefalopatias , Imagem por Ressonância Magnética , Assistência ao Paciente , Substância Branca
17.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762611

RESUMO

Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates and infants with an incidence of one in 2,000 to one in 4,000 newborns. Primary CH can be caused by thyroid dysgenesis and thyroid dyshormonogenesis. CH due to a TG gene mutation is one cause of thyroid dyshormonogenesis and can be characterized by goitrous CH with absent or low levels of serum thyroglobulin (Tg). In the present case, a 15-day-old neonate was referred to us with elevated thyroid stimulating hormone detected during a neonatal screening test. At the age of 34 months, extensive genetic testing was performed, including targeted exome sequencing for hypothyroidism, and revealed compound heterozygous mutations in the TG gene. Sanger sequencing of both parents’ DNA samples revealed a c.3790T> C (p.Cys1264Arg) mutation located at exon 17 inherited from the mother, and a c.4057C> T (p.Gln1353*) mutation located at exon 19 was inherited from the father. The c.4057C> T (p.Gln1353*) mutation located at exon 19 has never been reported and, therefore, is a new discovery. We report a case of primary permanent CH with compound heterozygous mutations of the TG gene, including a novel mutation.


Assuntos
Hipotireoidismo Congênito , DNA , Exoma , Éxons , Pai , Testes Genéticos , Humanos , Hipotireoidismo , Incidência , Lactente , Recém-Nascido , Mães , Triagem Neonatal , Tireoglobulina , Disgenesia da Tireoide , Glândula Tireoide , Tireotropina
18.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762440

RESUMO

BACKGROUND: von Willebrand disease (VWD), characterized by quantitative or qualitative defects of von Willebrand factor (VWF), is the most common inheritable bleeding disorder. Data regarding the genetic background of VWD in Korean patients is limited. To our knowledge, this is the first comprehensive molecular genetic investigation of Korean patients with VWD. METHODS: Twenty-two unrelated patients with VWD were recruited from August 2014 to December 2017 (age range 28 months–64 years; male:female ratio 1.2:1). Fifteen patients had type 1, six had type 2, and one had type 3 VWD. Blood samples were collected for coagulation analyses and molecular genetic analyses from each patient. Direct sequencing of all exons, flanking intronic sequences, and the promoter of VWF was performed. In patients without sequence variants, multiplex ligation-dependent probe amplification (MLPA) was performed to detect dosage variants. We adapted the American College of Medical Genetics and Genomics guidelines for variant interpretation and considered variants of uncertain significance, likely pathogenic variants, and pathogenic variants as putative disease-causing variants. RESULTS: VWF variants were identified in 15 patients (68%): 14 patients with a single heterozygous variant and one patient with two heterozygous variants. The variants consisted of 13 missense variants, one small insertion, and one splicing variant. Four variants were novel: p.S764Efs*16, p.C889R, p.C1130Y, and p.W2193C. MLPA analysis in seven patients without reportable variants revealed no dosage variants. CONCLUSIONS: This study revealed the spectrum of VWF variants, including novel ones, and limited diagnostic utility of MLPA analyses in Korean patients with VWD.


Assuntos
Éxons , Patrimônio Genético , Genética Médica , Genômica , Hemorragia , Humanos , Íntrons , Coreia (Geográfico) , Biologia Molecular , Reação em Cadeia da Polimerase Multiplex , Doença de von Willebrand Tipo 3 , Doenças de von Willebrand , Fator de von Willebrand
19.
Neonatal Medicine ; : 240-245, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-786434

RESUMO

Baller-Gerold syndrome is a rare autosomal recessive disorder characterized by premature fusion of the cranial sutures and malformation of the upper limb extremities at birth. Although the pathogenesis of Baller-Gerold Syndrome is not fully understood, it is mainly caused by mutations in the RecQ like helicase 4 (RECQL4) gene located on chromosome 8q24.3, which encodes the RECQL4 protein involved in normal DNA replication and repair. This study reports the case of a female premature infant with craniosynostosis of bilateral coronal sutures, resulting in a dysmorphic face and hypoplastic thumbs on both hands at birth, which are consistent with the core characteristics of Baller-Gerold syndrome. Diagnostic whole exome sequencing of the patient revealed a homozygous deletion from exon 13 to 18 in the RECQL4 gene. To the best of my knowledge, this is the first reported case of Baller-Gerold syndrome with RECQL4 gene mutation confirmed by diagnostic whole exome sequencing in Korea.


Assuntos
Suturas Cranianas , Craniossinostoses , Replicação do DNA , Exoma , Éxons , Extremidades , Feminino , Mãos , Deformidades da Mão , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Coreia (Geográfico) , Parto , Suturas , Polegar , Extremidade Superior
20.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-786129

RESUMO

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. Management of GIST patients is currently based on clinicopathological features and associated genetic changes. However, the detailed characteristics and molecular genetic features of GISTs have not yet been described in the Vietnamese population.METHODS: We first identified 155 patients with primary GIST who underwent surgery with primary curative intent between 2011 and 2014 at University Medical Center at Ho Chi Minh City, Vietnam. We evaluated the clinicopathological features and immunohistochemical reactivity to p53 and Ki-67 in these patients. Additionally, KIT genotyping was performed in 100 cases.RESULTS: The largest proportion of GISTs was classified as high-risk (43.2%). Of the 155 GISTs, 52 (33.5%) were positive for Ki-67, and 58 (37.4%) were positive for p53. The expression of Ki-67 and p53 were correlated with mitotic rate, tumor size, risk assessment, and tumor stage. Out of 100 GIST cases, KIT mutation was found in 68%, of which 62 (91.2%) were found in exon 11, two (2.9%) in exon 9, and four (5.8%) in exon 17. No mutation in exon 13 was identified. Additionally, KIT mutations did not correlate with any clinicopathological features.CONCLUSIONS: The expression of Ki-67 and p53 were associated with high-risk tumors. Mutations in exon 11 were the most commonly found, followed by exon 17 and exon 9. Additionally, KIT mutation status was not correlated with any recognized clinicopathological features.


Assuntos
Centros Médicos Acadêmicos , Grupo com Ancestrais do Continente Asiático , Éxons , Tumores do Estroma Gastrointestinal , Trato Gastrointestinal , Humanos , Biologia Molecular , Medição de Risco , Vietnã
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA