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Purpose@#Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant diseases caused by heterozygous mutation in the NF1 gene. Mutation detection is complex owing to the large size of the NF1 gene, the presence of a high number of partial pseudogenes, and the great variety of mutations. We aimed to study the mutation spectrum of NF1 gene in Korean patients with NF1. @*Materials and Methods@#We have analyzed total 69 unrelated patients who were clinically diagnosed with NF1. PCR and sequencing of the NF1 gene was performed in all unrelated index patients. Additionally, multiplex ligation-dependent probe amplification (MLPA) test of the NF1 and SPRED1 gene analysis (sequencing and MLPA test) were performed in patients with negative results from NF1 gene sequencing analysis. @*Results@#Fifty-five different variants were identified in 60 individuals, including six novel variants. The mutations included 36 single base substitutions (15 missense and 21 nonsense), eight splicing mutations, 13 small insertion or deletions, and three gross deletions. Most pathogenic variants were unique. The mutations were evenly distributed across exon one through 58 of NF1, and no mutational hot spots were found. When fulfilling the National Institutes of Health criterion for the clinical diagnosis of NF1, the detection rate was 84.1%. Cafe-au-lait macules were observed in all patients with NF1 mutations. There is no clear relationship between specific mutations and clinical features. @*Conclusion@#This study revealed a wide spectrum and genetic basis of patients with NF1 in Korea. Our results aim to contribute genetic management and counseling.
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Background@#We compared preoperative residual gastric volume (GV) between the first and second stages of total knee arthroplasty (TKA) in older adults after drinking carbohydrate-containing fluid 2 h prior to surgery. @*Methods@#In this study, 36 patients, aged > 65 years, scheduled for staged bilateral TKA with one-week interval, were enrolled. The patients consumed 400 ml of carbohydrate-containing fluid 2 h prior to surgery. Before the induction of spinal anesthesia, the gastric antral cross-sectional area was measured at the first and second TKA using ultrasound, and the residual GV was calculated. The primary outcome was the residual GV. Qualitative GV (grades 0, 1, and 2) and analgesic consumption after the first TKA were assessed as secondary outcomes. @*Results@#The GV (median [Q1, Q3]) was greater in the second-stage TKA (41.1 [22.5, 62.8] ml) than in the first-stage TKA (10.3 [0.0, 27.1] ml) (P < 0.001). In the qualitative assessment, the distribution was not different between the two stages of TKA (P = 0.219) and only one patient showed grade 2 gastric content in the second TKA. When opioid consumption was converted to an equivalent dose of morphine, an average of 53.9 mg of morphine was required after the first TKA. @*Conclusions@#Residual GV after drinking carbohydrate-containing fluid differed according to the stage of TKA, showing a larger residual GV in the second TKA than in the first one. In older adults scheduled to undergo bilateral staged TKA, caution is required in preoperative fasting practice, especially in second-stage surgery.
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BACKGROUND@#Genetic counseling (GC) provides many benefits, including the identification of patients appropriate for testing, patient education, and medical management. We evaluated the current status of and challenges faced by GC practitioners in Korean hospitals.@*METHODS@#An electronic survey was designed and conducted in 52 certified laboratory physicians belonging to the Korean Society of Laboratory Medicine, from August to September 2018. The questionnaires addressed three main categories of information: (1) current status of GC in hospitals; (2) essential qualifications of GC practitioners; and (3) challenges and perspectives for GC. Fisher's exact test was applied to analyze categorical data.@*RESULTS@#Among a total of 52 participants who initially responded, 12 (23.1%) were performing GC either by direct or indirect care. GC clinics were opened regularly for one (33.3%) or more than three sessions (25.0%) per week; most respondents spent more time for pre-visit activities than in-person visits, both for a initial visit patient and for a follow-up visit patient. All laboratory physicians provided genetic information to their patients. Most recommended family genetic testing when indicated (91.7%), discussed disease management (75.0%), and/or ordered additional genetic testing (58.3%), and some referred patients to other specialists (8.3%).@*CONCLUSIONS@#Both patients and laboratory physicians concede the advantage of GC performed by clinical geneticists; however, the practice of GC involves several challenges and raises some concerns. The cost and support required to implement GC need to be addressed in order to provide qualified GC in Korea.
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The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is increasing globally. However, a few studies have addressed their epidemiology in Seoul, Korea. In this study, we conducted one-year surveillance of CRE among 1,468 clinical isolates of Enterobacteriaceae at the hospital in Seoul with molecular characterization of carbapenemase genes. About 85% of CRE-positive samples were isolated from the elderly age group (above 60 years). The most common isolated organisms were Klebsiella pneumoniae (K. pneumoniae) (56.5%) and Escherichia coli (E.coli) (17.0%). We detected six different Carbapenemase-producing Enterobacteriaceae (CPE) of blaKPC, blaNDM, blaOXA, blaVIM, blaIMP, and blaGES alone or in combination with other bla genes. Typically, 853 (58.1%) isolates were tested positive for at least one CPE. KPC (K. pneumoniae carbapenemase)-2 was the most common CPE type (46.0%) followed by NDM (New Delhi metallo-β-lactamase)-1 (5.9%). KPC-2 was most commonly found in K. pneumoniae (494/676 isolates [73.1%]) and E.coli (107/676 isolates [15.8%]), whereas NDM-1 was commonly found in Enterobacter cloacae complex (20/86 isolates [23.3%]). Detailed information and molecular characteristics of CPE is essential to prevent the spread of these pathogens.
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Thrombophilia refers to inherited or acquired hemostatic disorders that result in a predisposition to blood clot formation. When combined with the hypercoagulable state that is characteristic of pregnancy, there is an increased risk of severe and recurrent pregnancy complications. Activated protein C resistance caused by factor V Leiden (FVL) mutation is known to be the most common cause of inherited thrombophilia in Caucasian population. FVL mutation has been related to pregnancy complications associated with hypercoagulation, e.g. miscarriage, intrauterine fetal demise, placental abruption, and intrauterine growth retardation. Although the FVL mutation is easily detected using molecular DNA techniques, patients who are heterozygous for this disorder often remain asymptomatic until they develop a concurrent prothrombotic condition. Because there are potentially serious effects of FVL mutation for pregnancy, and because effective treatment strategies exist, early detection and treatment of this condition might be considered.
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Feminino , Humanos , Gravidez , Aborto Espontâneo , Descolamento Prematuro da Placenta , Resistência à Proteína C Ativada , DNA , Fator V , Morte Fetal , Retardo do Crescimento Fetal , Transtornos Hemostáticos , Complicações na Gravidez , Gestantes , TrombofiliaRESUMO
Legionella species are abundant in the built environment and are increasingly recognized as a cause of Legionnaires' disease (LD). As the number of cases of Legionnaires' disease acquired by local communities in the Seoul metropolitan area in Korea has been increased, there was concern that changes in environmental factors could affect disease outbreaks. We described the association between climatic variables and occurrence of legionellosis in Korea and Legionella detection rate in Seoul area. A total of 418 cases of legionellosis were reported between 2014 and 2017. There was a seasonal peak in summer. LD continuously occurred from early spring to winter every year and rapidly increased in summer. In the regression analysis, the primary variables of interest- PM2.5 (µg/m³), NO₂ (ppb), and a number of the date of issue O₃ warning were not significant except for average temperature (R²=0.8075). The Legionella detection rate in Seoul, Korea showed a trend similar to precipitation (P=0.708, ANOVA). A relatively high proportion of Legionella detection rate was shown, especially cooling tower (17.7%) and public bath (19.3%). This finding is in line with current understanding of the ecological profile of this pathogen and supports the assertion that legionellosis occurs through contamination of water sources.
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Banhos , Surtos de Doenças , Epidemiologia , Coreia (Geográfico) , Legionella , Legionelose , Doença dos Legionários , Análise de Regressão , Estações do Ano , Seul , ÁguaRESUMO
BACKGROUND: Chromosomal abnormalities are confirmed as one of the frequent causes of male infertility. The microdeletion of the azoospermia factor (AZF) region in the Y chromosome was discovered as another frequent genetic cause associated with male infertility. The aim of this study was to evaluate the frequency and type of chromosomal abnormalities and Y chromosome microdeletions in Korean infertile men. METHODS: A total of 846 infertile men with azoospermia and severe oligozoospermia were included for genetic screening. Cytogenetic analyses using G-banding and screening for Y chromosome microdeletions by multiplex PCR for AZF genes were performed. RESULTS: Chromosomal abnormalities were detected in 112 infertile men (13.2%). Of these, Klinefelter's syndrome was the most common (55.4%, 62/112), followed by balanced translocation including translocation between sex chromosome and autosome (14.3%), Yq deletion (13.4%), X/XY mosaicism with Yq deletion (12.5%), and XX male (4.5%). The overall prevalence of Y chromosome microdeletions was 9.2% (78/846). Most microdeletions were in the AZFc region (51.3%) with a low incidence in AZFa (7.7 %) and AZFb (6.4 %). Combined deletions involving the AZFbc and AZFabc regions were detected in 26.9 % and 7.7 % of men, respectively. Among the infertile men with Y chromosome microdeletions, the incidence of chromosomal abnormality was 25.6% (20/78). CONCLUSIONS: There was a high incidence (20.1%) of chromosomal abnormalities and Y chromosome microdeletions in Korean infertile men. These findings strongly suggest that genetic screening for chromosomal abnormalities and Y chromosome microdeletions should be performed, and genetic counseling should be provided before starting assisted reproductive techniques.
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Humanos , Masculino , Azoospermia , Aberrações Cromossômicas , Análise Citogenética , Aconselhamento Genético , Testes Genéticos , Incidência , Infertilidade Masculina , Síndrome de Klinefelter , Programas de Rastreamento , Mosaicismo , Reação em Cadeia da Polimerase Multiplex , Oligospermia , Prevalência , Técnicas de Reprodução Assistida , Cromossomos Sexuais , Cromossomo YRESUMO
Diarrheagenic Escherichia coli (E. coli) is a main cause of diarrhea worldwide. This study reports the investigation on the occurrence of enterotoxigenic E. coli (ETEC) serotype O27:H7-associated foodborne gastrointestinal disease that occurred at two schools, one middle school and one high school, in Seoul, Korea in June 2015. The immediate government investigation in 1,216 students and 19 food handlers in these two schools revealed that 116 students, 32 students in the middle school and 84 students in the high school, and 2 food handlers, one from middle school and the other from high school, developed gastrointestinal illness symptoms including diarrhea. Following lab investigation identified 29 ETEC serotype O27:H7 strains, 27 from 116 students and 2 from 19 food handlers. Pattern of pulsed-field gel electrophoresis analysis of ETEC isolates suggested that ETEC serotype O27:H7 caused the diarrheal outbreak in June 2015 in Seoul, Korea was a specific clone. In addition, these ETEC serotype O27:H7 isolates were highly resistance to the several antibiotics. The results from the present study provide the evidence that ETEC serotype O27:H7 can be an important cause of domestic foodborne outbreak in Korea.
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Humanos , Antibacterianos , Células Clonais , Diarreia , Eletroforese em Gel de Campo Pulsado , Escherichia coli Enterotoxigênica , Escherichia coli , Gastroenteropatias , Coreia (Geográfico) , Seul , SorogrupoRESUMO
BACKGROUND/OBJECTIVES: Constipation is a condition that can result from intestinal deformation. Because humans have an upright posture, the effects of gravity can cause this shape deformation. Oligosaccharides are common prebiotics and their effects on bowel health are well known. However, studies of the physiological functionality of a product that contains both lactulose and galactooligosaccharides are insufficient. We investigated the constipation reduction effect of a dual-type oligosaccharide, Dual-Oligo, in loperamide-treated rats. MATERIALS/METHODS: Dual-Oligo consists of galactooligosaccharides (15.80%) and lactulose (51.67%). Animals were randomly divided into four groups, the normal group (normal), control group (control), low concentration of Dual-Oligo (LDO) group, and high concentration of Dual-Oligo (HDO) group. After 7 days of oral administration, fecal pellet amount, fecal weight, water content of fecal were measured. Blood chemistry, short-chain fatty acid (SCFA), gastrointestinal transit ratio and length and intestinal mucosa were analyzed. RESULTS: Dual-Oligo increased the fecal weight, and water content of feces in rats with loperamide-induced constipation. Gastrointestinal transit ratio and length and area of intestinal mucosa significantly increased after treatment with Dual-Oligo in loperamide-induced rats. A high concentration of Dual-Oligo tended to produce more acetic acid than that observed for the control group, and Dual-Oligo affected the production of total SCFA. Bifidobacteria concentration of cecal contents in the high-concentration oligosaccharide (HDO) and low-concentration oligosaccharide (LDO) groups was similar to the result of the normal group. CONCLUSIONS: These results showed that Dual-Oligo is a functional material that is derived from a natural food product and is effective in ameliorating constipation.
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Animais , Humanos , Ratos , Ácido Acético , Administração Oral , Azul Alciano , Química , Constipação Intestinal , Fezes , Trânsito Gastrointestinal , Gravitação , Mucosa Intestinal , Lactulose , Loperamida , Oligossacarídeos , Postura , Prebióticos , ÁguaRESUMO
No abstract available.
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Criança , Humanos , Masculino , Bandeamento Cromossômico , Deleção Cromossômica , Cromossomos Humanos Par 4/genética , Hibridização Genômica Comparativa , Deficiências do Desenvolvimento/diagnóstico , Deleção de SequênciaRESUMO
PURPOSE: Conventional methods for the prenatal detection of fetal RhD status involve invasive procedures such as fetal blood sampling and amniocentesis. The identification of cell-free fetal DNA (cffDNA) in maternal plasma creates the possibility of determining fetal RhD status by analyzing maternal plasma DNA. However, some technical problems still exist, especially the lack of a positive control marker for the presence of fetal DNA. Therefore, we assessed the feasibility and accuracy of fetal RHD genotyping incorporating the RASSF1A epigenetic fetal DNA marker from cffDNA in the maternal plasma of RhD-negative pregnant women in Korea. MATERIALS AND METHODS: We analyzed maternal plasma from 41 pregnant women identified as RhD-negative by serological testing. Multiplex real-time PCR was performed by amplifying RHD exons 5 and 7 and the SRY gene, with RASSF1A being used as a gender-independent fetal epigenetic marker. The results were compared with those obtained by postnatal serological analysis of cord blood and gender identification. RESULTS: Among the 41 fetuses, 37 were RhD-positive and 4 were RhD-negative according to the serological analysis of cord blood. There was 100% concordance between fetal RHD genotyping and serological cord blood results. Detection of the RASSF1A gene verified the presence of cffDNA, and the fetal SRY status was correctly detected in all 41 cases. CONCLUSION: Noninvasive fetal RHD genotyping with cffDNA incorporating RASSF1A is a feasible, reliable, and accurate method of determining fetal RhD status. It is an alternative to amniocentesis for the management of RhD-negative women and reduces the need for unnecessary RhIG prophylaxis.
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Feminino , Humanos , Amniocentese , DNA , Epigenômica , Éxons , Sangue Fetal , Feto , Genes sry , Marcadores Genéticos , Coreia (Geográfico) , Plasma , Gestantes , Diagnóstico Pré-Natal , Reação em Cadeia da Polimerase em Tempo Real , Testes SorológicosRESUMO
PURPOSE: Noninvasive prenatal test (NIPT) by massively parallel sequencing (MPS) of cell-free fetal DNA in maternal plasma marks a significant advancement in prenatal screening, minimizing the need for invasive testing of fetal chromosomal aneuploidies. Here, we report the initial clinical performance of NIPT in Korean pregnant women. MATERIALS AND METHODS: MPS-based NIPT was performed on 910 cases; 5 mL blood samples were collected and sequenced in the Shenzhen BGI Genomic Laboratory to identify aneuploidies. The risk of fetal aneuploidy was determined by L-score and t-score, and classified as high or low. The NIPT results were validated by karyotyping for the high-risk cases and neonatal follow-up for low-risk cases. RESULTS: NIPT was mainly requested for two clinical indications: abnormal biochemical serum-screening result (54.3%) and advanced maternal age (31.4%). Among 494 cases with abnormal biochemical serum-screening results, NIPT detected only 9 (1.8%) high-risk cases. Sixteen cases (1.8%) of 910 had a high risk for aneuploidy: 8 for trisomy 21, 2 for trisomy 18, 1 for trisomy 13, and 5 for sex chromosome abnormalities. Amniocentesis was performed for 7 of these cases (43.8%). In the karyotyping and neonatal data, no false positive or negative results were observed in our study. CONCLUSION: MPS-based NIPT detects fetal chromosomal aneuploidies with high accuracy. Introduction of NIPT as into clinical settings could prevent about 98% of unnecessary invasive diagnostic procedures.
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Feminino , Humanos , Amniocentese , Aneuploidia , DNA , Síndrome de Down , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala , Cariotipagem , Coreia (Geográfico) , Idade Materna , Plasma , Gestantes , Diagnóstico Pré-Natal , Aberrações dos Cromossomos Sexuais , TrissomiaRESUMO
The risk of developing colorectal cancer is increased in patients with inflammatory bowel disease. Surveillance colonoscopy has not been shown to prolong survival and rates of interval cancer are reported to be high. Continuing colonic inflammation has been shown to be important in the development of colorectal cancer and therefore anti-inflammatory agents such as the 5-aminosalicylates and immunomodulators have been considered as potential chemopreventive agents. This review focuses on various chemopreventive agents that have been clearly shown to reduce the risk of colorectal adenoma and cancer in the patients with inflammatory bowel disease.
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Anti-Inflamatórios/uso terapêutico , Quimioprevenção , Neoplasias Colorretais/complicações , Ácido Fólico/uso terapêutico , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Mesalamina/uso terapêutico , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
PURPOSE: The mutation of the SLC26A4 gene is the second most common cause of congenital hearing loss after GJB2 mutations. It has been identified as a major cause of autosomal recessive nonsyndromic hearing loss associated with enlarged vestibular aqueduct and Pendred syndrome. Although most studies of SLC26A4 mutations have dealt with hearing-impaired patients, there are a few reports on the frequency of these mutations in the general population. The purpose of this study was to evaluate the prevalence of SLC26A4 mutations that cause inherited deafness in the general Korean population. MATERIALS AND METHODS: We obtained blood samples from 144 Korean individuals with normal hearing. The samples were subjected to polymerase chain reaction to amplify the entire coding region of the SLC26A4 gene, followed by direct DNA sequencing. RESULTS: Sequencing analysis of this gene identified 5 different variants (c.147C>G, c.225G>C, c.1723A>G, c.2168A>G, and c.2283A>G). The pathogenic mutation c.2168A>G (p.H723R) was identified in 1.39% (2/144) of the subjects with normal hearing. CONCLUSION: These data provide information about carrier frequency for SLC26A4 mutation-associated hearing loss and have important implications for genetic diagnostic testing for inherited deafness in the Korean population.
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Humanos , Codificação Clínica , Surdez , Testes Diagnósticos de Rotina , Audição , Perda Auditiva , Reação em Cadeia da Polimerase , Prevalência , Análise de Sequência de DNA , Aqueduto VestibularRESUMO
BACKGROUND: Despite the great potential of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) in the cardiac cell transplantation, the low graft survival still remains as one of the main obstacles in the way to its clinical application. We investigated whether pre-treatment with isoflurane can decrease apoptosis of hESC-derived CPCs under oxidative stress. METHODS: Undifferentiated hESCs were differentiated in suspension media with 20% fetal bovine serum (FBS) and 20 ng/ml of bone morphogenetic protein (BMP)-4 through embryoid bodies and grown onto Matrigel-coated plates for 2 or 3 weeks. To identify the differentiated CPCs, immunostaining for nonspecific transcriptional marker (Nkx2.5) was performed. The CPCs were exposed to oxidative stress induced by Fenton reaction with H2O2 and FeSO4. For anesthetic preconditioning, CPCs were exposed to isoflurane (5 vol%) in an isolated chamber. Apoptosis of CPCs was determined by TUNEL staining and detection of activated caspase-3 cell. RESULTS: hESC-derived CPCs stained with Nkx2.5 were 95 +/- 3% of total cell number. Concentration of isoflurane in the media was 1.1 mM (2.2 MAC). Pretreatment of CPCs with isoflurane showed a significantly lower TUNEL (+) ratio as well as activated caspase-3 cell number compared to control. CONCLUSIONS: Isoflurane decreased hESC-derived Nkx2.5+ CPCs apoptosis induced by oxidative stress. This result suggests that anti-apoptotic effect may play a role in the protective effect of isoflurane.
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Humanos , Apoptose , Proteínas Morfogenéticas Ósseas , Caspase 3 , Contagem de Células , Transplante de Células , Corpos Embrioides , Células-Tronco Embrionárias , Sobrevivência de Enxerto , Marcação In Situ das Extremidades Cortadas , Isoflurano , Estresse Oxidativo , Células-Tronco , TransplantesRESUMO
No abstract available.
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Feminino , Humanos , Pessoa de Meia-Idade , Antineoplásicos/uso terapêutico , Células da Medula Óssea/patologia , Cladribina/uso terapêutico , Análise Mutacional de DNA , Imunofenotipagem , Leucemia de Células Pilosas/diagnóstico , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Reticulina/metabolismoRESUMO
PURPOSE: Fragile X carrier detection before or at early pregnancy through a wide screening program may not only confer a risk of having offspring with Fragile X syndrome (FXS), but may also confer a risk for Fragile X-associated primary ovarian insufficiency and Fragile X-associated tremor/ataxia syndrome. However, prior to the implementation of such a program, the carrier prevalence in a population and the availability of effective screening test should be evaluated. The aim of our study was to determine the prevalence of premutation carriers and to evaluate the feasibility of screening test. MATERIALS AND METHODS: The blood samples were obtained from 8,641 pregnant women with no family history of mental retardation. We performed a three-primer CGG repeat primed (RP) PCR using the AmplideX(TM) FMR1 PCR kit (Asuragen, Inc. Austin, TX, USA). Samples showing full mutation alleles were reflexed to Southern blot analysis for methylation status and sizing. RESULTS: Among the 8,641 women, we found 8 premutation carriers (1:1,090, 0.09%) and 46 women with an intermediate allele (1:190, 0.53%). No woman was found to carry the fully mutated allele. All the detected alleles were within the CGG repeat range of 8-117. Among the 8,641 samples, 29 and 30 CGG repeats represent 66.6% of all cases. The CGG RP PCR method provides robust detection of expanded alleles and resolves allele zygosity, thus minimizing the number of samples that require Southern blot analysis. CONCLUSION: This is the first study that has focused on the prevalence of FXS premutation carriers and FMR1 allele distribution in normal pregnant women. These data have important implications for population-based fragile X carrier screening in Korea.
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Feminino , Humanos , Gravidez , Alelos , Southern Blotting , Síndrome do Cromossomo X Frágil , Deficiência Intelectual , Coreia (Geográfico) , Programas de Rastreamento , Metilação , Reação em Cadeia da Polimerase , Gestantes , Prevalência , Insuficiência Ovariana Primária , Reflexo , TerpenosRESUMO
PURPOSE: Fragile X carrier detection before or at early pregnancy through a wide screening program may not only confer a risk of having offspring with Fragile X syndrome (FXS), but may also confer a risk for Fragile X-associated primary ovarian insufficiency and Fragile X-associated tremor/ataxia syndrome. However, prior to the implementation of such a program, the carrier prevalence in a population and the availability of effective screening test should be evaluated. The aim of our study was to determine the prevalence of premutation carriers and to evaluate the feasibility of screening test. MATERIALS AND METHODS: The blood samples were obtained from 8,641 pregnant women with no family history of mental retardation. We performed a three-primer CGG repeat primed (RP) PCR using the AmplideX(TM) FMR1 PCR kit (Asuragen, Inc. Austin, TX, USA). Samples showing full mutation alleles were reflexed to Southern blot analysis for methylation status and sizing. RESULTS: Among the 8,641 women, we found 8 premutation carriers (1:1,090, 0.09%) and 46 women with an intermediate allele (1:190, 0.53%). No woman was found to carry the fully mutated allele. All the detected alleles were within the CGG repeat range of 8-117. Among the 8,641 samples, 29 and 30 CGG repeats represent 66.6% of all cases. The CGG RP PCR method provides robust detection of expanded alleles and resolves allele zygosity, thus minimizing the number of samples that require Southern blot analysis. CONCLUSION: This is the first study that has focused on the prevalence of FXS premutation carriers and FMR1 allele distribution in normal pregnant women. These data have important implications for population-based fragile X carrier screening in Korea.
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Feminino , Humanos , Gravidez , Alelos , Southern Blotting , Síndrome do Cromossomo X Frágil , Deficiência Intelectual , Coreia (Geográfico) , Programas de Rastreamento , Metilação , Reação em Cadeia da Polimerase , Gestantes , Prevalência , Insuficiência Ovariana Primária , Reflexo , TerpenosRESUMO
Owing to the risk of fetal loss associated with prenatal diagnostic procedures (amniocentesis, chorionic villus sampling), noninvasive prenatal diagnosis (NIPD) is ultimate goal of prenatal diagnosis. The discovery of circulating cell-free fetal DNA (cffDNA) in maternal plasma in 1997 has opened up new probabilities for NIPD by Dr. Lo et al. The last decade has seen great development in NIPD. Fetal sex and fetal RhD status determination by cffDNA analysis is already in clinical use in certain countries. For routine use, this test is limited by the amount of cell-free maternal DNA in blood sample, the lack of universal fetal markers, and appropriate reference materials. To improve the accuracy of detection of fetal specific sequences in maternal plasma, internal positive controls to confirm to presence of fetal DNA should be analyzed. We have developed strategies for noninvasive determination of fetal gender, and fetal RhD genotyping using cffDNA in maternal plasma, using real-time quantitative polymerase chain reaction (RT-PCR) including RASSF1A epigenetic fetal DNA marker (gender-independent) as internal positive controls, which is to be first successful study of this kind in Korea. In our study, accurate detection of fetal gender through gestational age, and fetal RhD genotyping in RhD-negative pregnant women was achieved. In this assay, we show that the assay is sensitive, easy, fast, and reliable. These developments improve the reliability of the applications of circulating fetal DNA when used in clinical practice to manage sex-linked disorders (e.g., hemophilia, Duchenne muscular dystrophy), congenital adrenal hyperplasia (CAH), RhD incompatibility, and the other noninvasive pregnant diagnostic tests on the coming soon. The study was the first successful case in Korea using cffDNA in maternal plasma, which has created a new avenue for clinical applications of NIPD.
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Feminino , Humanos , Hiperplasia Suprarrenal Congênita , Vilosidades Coriônicas , Colódio , Testes Diagnósticos de Rotina , DNA , Epigenômica , Marcadores Genéticos , Idade Gestacional , Hemofilia A , Coreia (Geográfico) , Plasma , Reação em Cadeia da Polimerase , Gestantes , Diagnóstico Pré-NatalRESUMO
Red cell antigens, A, B, and H can be weakened or lost especially in patients with hematologic malignancies. We report a 42-year-old female patient with acute myeloid leukemia, who showed loss of A antigen on her red cells. She showed the persistence of leukemia in spite of three cycles of induction chemotherapy. Her ABO blood group showed a discrepancy: the cell type was O and the serum type was A. Adsorption/elution test could not identify the presence of A antigen on her red cells, and the test for A and B transferases was negative. ABO genotyping using PCR/restriction fragment length polymorphism and sequencing of exons 6 and 7 of the ABO gene demonstrated 467 C>T substitution in exon 7 and confirmed the genotype of A102/O01. She was transfused with leukapheresis products collected from donors with blood group A, but expired of severe sepsis. This is the first Korean case, in which red cell A antigen loss was genetically proven using sequencing, and underscores the necessity of ABO genotyping to solve the ABO discrepancy and to transfuse effectively.