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1.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474058

RESUMO

Chimerism monitoring following allogeneic hematopoietic cell transplantation (HCT) plays a pivotal role in evaluating engraftment status and identifying early indicators of relapse. Recent advancements in next-generation sequencing (NGS) technology have introduced AlloSeq HCT as a more sensitive alternative to short tandem repeat (STR) analysis. This study aimed to compare AlloSeq HCT with STR, focusing on the prediction of early relapse post-allogeneic HCT. Chimerism levels in 29 HCT recipients were assessed using both STR and NGS, employing a total of 125 whole blood or bone marrow aspirate samples (68 post-HCT and 57 pre-HCT samples from recipients or donors). AlloSeq HCT exhibited high concordance with STR and demonstrated the potential for early detection of chimeric changes, particularly at extremely low levels. The combined advantages of high sensitivity and automated data analysis offered by AlloSeq HCT substantiate its clinical adoption for effective chimerism monitoring.


Assuntos
Quimerismo , Transplante de Células-Tronco Hematopoéticas , Humanos , Quimeras de Transplante , Doença Crônica , Recidiva , Sequenciamento de Nucleotídeos em Larga Escala
2.
BMC Bioinformatics ; 24(1): 62, 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36823555

RESUMO

Internal tandem duplication (ITD) of the FMS-like tyrosine kinase (FLT3) gene is associated with poor clinical outcomes in patients with acute myeloid leukemia. Although recent methods for detecting FLT3-ITD from next-generation sequencing (NGS) data have replaced traditional ITD detection approaches such as conventional PCR or fragment analysis, their use in the clinical field is still limited and requires further information. Here, we introduce ITDetect, an efficient FLT3-ITD detection approach that uses NGS data. Our proposed method allows for more precise detection and provides more detailed information than existing in silico methods. Further, it enables FLT3-ITD detection from exome sequencing or targeted panel sequencing data, thereby improving its clinical application. We validated the performance of ITDetect using NGS-based and experimental ITD detection methods and successfully demonstrated that ITDetect provides the highest concordance with the experimental methods. The program and data underlying this study are available in a public repository.


Assuntos
Leucemia Mieloide Aguda , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Humanos , Proteínas Tirosina Quinases/genética , Sequências de Repetição em Tandem/genética , Leucemia Mieloide Aguda/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Tirosina Quinase 3 Semelhante a fms/genética , Mutação , Duplicação Gênica
3.
Genet Med ; 24(3): 663-672, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34906491

RESUMO

PURPOSE: Despite the importance of exonic copy number variations (CNVs) in human genetic diseases, reliable next-generation sequencing-based methods for detecting them are unavailable. We developed an expandable and robust exonic CNV detection tool called consistent count region (CCR)-CNV. METHODS: In total, about 1000 samples of the truth set were used for validating CCR-CNV. We compared CCR-CNV performance with 2 well-known CNV tools. Finally, to overcome the limitations of CCR-CNV, we devised a combined approach. RESULTS: The mean sensitivity and specificity of CCR-CNV alone were above 95%, which was superior to that of other CNV tools, such as DECoN and Atlas-CNV. However, low covered region and positive predictive value and high false discovery rate act as obstacles to its use in clinical settings. The combined approach showed much improved performance than CCR-CNV alone. CONCLUSION: In this study, we present a novel diagnostic tool that allows the identification of exonic CNVs with high confidence using various reagents and clinical next-generation sequencing platforms. We validated this method using the largest multiple ligation-dependent probe amplification-confirmed data set, including sufficient copy normal control data. The approach, combined with existing CNV tools, allows the implementation of CCR-CNV in clinical settings.


Assuntos
Variações do Número de Cópias de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Variações do Número de Cópias de DNA/genética , Éxons/genética , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos
4.
Clin Chem ; 68(12): 1509-1518, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36177751

RESUMO

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for early tumor detection and minimal residual disease (MRD) assessment in early-stage cancer, but quantifying minute amounts of ctDNA is challenging and well-designed studies on ctDNA in early-stage cancer are still lacking. Here, we adapted a sensitive next-generation sequencing (NGS) technology and performed parallel analysis of pre- and postoperative ctDNA and matched tumor tissues in a prospective cohort of patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: In total, 70 consecutive patients undergoing curative resection for resectable PDAC were enrolled. We performed integrated digital error suppression-enhanced cancer personalized profiling by deep sequencing NGS of triple-matched samples (pre/postoperative plasma cell-free DNA [cfDNA], tumor tissue, and genomic DNA) targeting 77 genes. RESULTS: Preoperative ctDNA was detected in 37.7% of the evaluable patients, with a median variant allele frequency of 0.09%. Twelve additional oncogenic mutations were detected exclusively in preoperative ctDNA but not in tissue. When quantitative concentrations of ctDNA were estimated in haploid genome equivalents per milliliter (hGE/mL), the risk of early recurrence was high in patients with postoperative ctDNA >1 hGE/mL. cfDNA variants from 24.5% of patients had features compatible with clonal hematopoiesis. CONCLUSIONS: An optimized NGS approach might add value beyond tissue analysis through the highly sensitive detection of minute amounts of ctDNA in resectable PDAC. Postoperative ctDNA concentration could be a tool for MRD assessment. Moreover, parallel analyses of matched tissues and leukocytes might be required to accurately detect clinically relevant ctDNA.


Assuntos
Adenocarcinoma , DNA Tumoral Circulante , Neoplasias Pancreáticas , Humanos , DNA Tumoral Circulante/genética , Estudos Prospectivos , Biomarcadores Tumorais , Mutação , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasia Residual , Neoplasias Pancreáticas
5.
Proteomics ; 21(11-12): e2000278, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33945677

RESUMO

In managing patients with coronavirus disease 2019 (COVID-19), early identification of those at high risk and real-time monitoring of disease progression to severe COVID-19 is a major challenge. We aimed to identify potential early prognostic protein markers and to expand understanding of proteome dynamics during clinical progression of the disease. We performed in-depth proteome profiling on 137 sera, longitudinally collected from 25 patients with COVID-19 (non-severe patients, n = 13; patients who progressed to severe COVID-19, n = 12). We identified 11 potential biomarkers, including the novel markers IGLV3-19 and BNC2, as early potential prognostic indicators of severe COVID-19. These potential biomarkers are mainly involved in biological processes associated with humoral immune response, interferon signalling, acute phase response, lipid metabolism, and platelet degranulation. We further revealed that the longitudinal changes of 40 proteins persistently increased or decreased as the disease progressed to severe COVID-19. These 40 potential biomarkers could effectively reflect the clinical progression of the disease. Our findings provide some new insights into host response to SARS-CoV-2 infection, which are valuable for understanding of COVID-19 disease progression. This study also identified potential biomarkers that could be further validated, which may support better predicting and monitoring progression to severe COVID-19.


Assuntos
COVID-19 , Interações Hospedeiro-Patógeno/genética , Proteoma , Transcriptoma/genética , Idoso , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/genética , COVID-19/metabolismo , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteoma/análise , Proteoma/genética , Proteoma/metabolismo , Proteômica
6.
Clin Infect Dis ; 73(9): e3002-e3008, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33219681

RESUMO

BACKGROUND: Positive results from real-time reverse-transcription polymerase chain reaction (rRT-PCR) in recovered patients raise concern that patients who recover from coronavirus disease 2019 (COVID-19) may be at risk of reinfection. Currently, however, evidence that supports reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reported. METHODS: We conducted whole-genome sequencing of the viral RNA from clinical specimens at the initial infection and at the positive retest from 6 patients who recovered from COVID-19 and retested positive for SARS-CoV-2 via rRT-PCR after recovery. A total of 13 viral RNAs from the patients' respiratory specimens were consecutively obtained, which enabled us to characterize the difference in viral genomes between initial infection and positive retest. RESULTS: At the time of the positive retest, we were able to acquire a complete genome sequence from patient 1, a 21-year-old previously healthy woman. In this patient, through the phylogenetic analysis, we confirmed that the viral RNA of positive retest was clustered into a subgroup distinct from that of the initial infection, suggesting that there was a reinfection of SARS-CoV-2 with a subtype that was different from that of the primary strain. The spike protein D614G substitution that defines the clade "G" emerged in reinfection, while mutations that characterize the clade "V" (ie, nsp6 L37F and ORF3a G251V) were present at initial infection. CONCLUSIONS: Reinfection with a genetically distinct SARS-CoV-2 strain may occur in an immunocompetent patient shortly after recovery from mild COVID-19. SARS-CoV-2 infection may not confer immunity against a different SARS-CoV-2 strain.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Feminino , Humanos , Filogenia , RNA Viral/genética , Reinfecção , Adulto Jovem
7.
Clin Infect Dis ; 71(16): 2236-2239, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32297925

RESUMO

We report changes in viral load over time in a 27-day-old neonate with coronavirus disease 2019 who presented with fever, cough, and vomiting. Severe acute respiratory syndrome coronavirus 2 RNA was detected in the nasopharynx, oropharynx, stool, saliva, plasma, and urine. The highest viral RNA copies in nasopharynx decreased over time while viral load in stool remained high.


Assuntos
COVID-19/diagnóstico , Mães , RNA Viral/análise , Carga Viral , Líquidos Corporais/virologia , COVID-19/sangue , COVID-19/urina , Fezes/virologia , Feminino , Humanos , Recém-Nascido , Coreia (Geográfico) , Nasofaringe/virologia , SARS-CoV-2 , Saliva/virologia
8.
Emerg Infect Dis ; 26(10): 2497-2499, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32497001

RESUMO

Along with positive SARS-CoV-2 RNA in nasopharyngeal swabs, viral RNA was detectable at high concentration for >3 weeks in fecal samples from 12 mildly symptomatic and asymptomatic children with COVID-19 in Seoul, South Korea. Saliva also tested positive during the early phase of infection. If proven infectious, feces and saliva could serve as transmission sources.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Fezes/virologia , Nasofaringe/virologia , Pneumonia Viral/virologia , RNA Viral/análise , Saliva/virologia , Adolescente , Infecções Assintomáticas , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/urina , Humanos , Lactente , Recém-Nascido , Pandemias , Plasma/virologia , Pneumonia Viral/transmissão , Pneumonia Viral/urina , República da Coreia , SARS-CoV-2 , Urina/virologia , Carga Viral
9.
Mov Disord ; 35(5): 868-876, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32039503

RESUMO

BACKGROUND: SNCA multiplication is a genomic cause of familial PD, showing dosage-dependent toxicity. Until now, nonallelic homologous recombination was suggested as the mechanism of SNCA duplication, based on various types of repetitive elements found in the spanning region of the breakpoints. However, the sequence at the breakpoint was analyzed only for 1 case. OBJECTIVES: We have analyzed the breakpoint sequences of 6 patients with PD who had duplicated SNCA using whole-genome sequencing data to elucidate the mechanism of SNCA duplication. METHODS: Six patient samples with SNCA duplication underwent whole-genome sequencing. The duplicated regions were defined with nucleotide-resolution breakpoints, which were confirmed by junction polymerase chain reaction and Sanger sequencing. The search for potential non-B DNA-forming sequences and stem-loop structure predictions was conducted. RESULTS: Duplicated regions ranged from the smallest region of 718.3 kb to the largest one of 4,162 kb. Repetitive elements were found at 8 of the 12 breakpoint sequences on each side of the junction, but none of the pairs shared overt homologies. Five of these six junctions had microhomologies (2-4 bp) at the breakpoint, and a short stretch of sequences was inserted in 3 cases. All except one junction were located within or next to stem-loop structures. CONCLUSION: Our study has determined that homologous recombination mechanisms involving repetitive elements are not the main cause of the duplication of SNCA. The presence of microhomology at the junctions and their position within stem-loop structures suggest that replication-based rearrangements may be a common mechanism for SNCA amplification. © 2020 International Parkinson and Movement Disorder Society.


Assuntos
Duplicação Gênica , Rearranjo Gênico , Doença de Parkinson , alfa-Sinucleína/genética , Humanos , Doença de Parkinson/genética
10.
BMC Genomics ; 20(1): 910, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783732

RESUMO

BACKGROUND: Mycoplasma pneumoniae is a common cause of respiratory tract infections in children and adults. This study applied high-throughput whole genome sequencing (WGS) technologies to analyze the genomes of 30 M. pneumoniae strains isolated from children with pneumonia in South Korea during the two epidemics from 2010 to 2016 in comparison with a global collection of 48 M. pneumoniae strains which includes seven countries ranging from 1944 to 2017. RESULTS: The 30 Korean strains had approximately 40% GC content and ranged from 815,686 to 818,669 base pairs, coding for a total of 809 to 828 genes. Overall, BRIG revealed 99% to > 99% similarity among strains. The genomic similarity dropped to approximately 95% in the P1 type 2 strains when aligned to the reference M129 genome, which corresponded to the region of the p1 gene. MAUVE detected four subtype-specific insertions (three in P1 type 1 and one in P1 type 2), of which were all hypothetical proteins except one tRNA insertion in all P1 type 1 strains. The phylogenetic associations of 30 strains were generally consistent with the multilocus sequence typing results. The phylogenetic tree constructed with 78 genomes including 30 genomes from Korea formed two clusters and further divided into two sub-clusters. eBURST analysis revealed two clonal complexes according to P1 typing results showing higher diversity among P1 type 2 strains. CONCLUSIONS: The comparative whole genome approach was able to define high genetic identity, unique structural diversity, and phylogenetic associations among the 78 M. pneumoniae strains isolated worldwide.


Assuntos
Genoma Bacteriano , Mycoplasma pneumoniae/genética , Proteínas de Bactérias/genética , Criança , Epidemias , Genômica , Humanos , Mutação INDEL , Mycoplasma pneumoniae/classificação , Mycoplasma pneumoniae/isolamento & purificação , Filogenia , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/microbiologia , Polimorfismo de Nucleotídeo Único , República da Coreia/epidemiologia
11.
J Med Genet ; 55(12): 794-802, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30415210

RESUMO

BACKGROUND: BRCA1 and BRCA2 (BRCA1/2) variants classified ambiguously as variants of uncertain significance (VUS) are a major challenge for clinical genetic testing in breast cancer; their relevance to the cancer risk is unclear and the association with the response to specific BRCA1/2-targeted agents is uncertain. To minimise the proportion of VUS in BRCA1/2, we performed the multifactorial likelihood analysis and validated this method using an independent cohort of patients with breast cancer. METHODS: We used a data set of 2115 patients with breast cancer from the nationwide multicentre prospective Korean Hereditary Breast Cancer study. In total, 83 BRCA1/2 VUSs (BRCA1, n=26; BRCA2, n=57) were analysed. The multifactorial probability was estimated by combining the prior probability with the overall likelihood ratio derived from co-occurrence of each VUS with pathogenic variants, personal and family history, and tumour characteristics. The classification was compared with the interpretation according to the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG/AMP) guidelines. An external validation was conducted using independent data set of 810 patients. RESULTS: We were able to redefine 38 VUSs (BRCA1, n=10; BRCA2, n=28). The revised classification was highly correlated with the ACMG/AMP guideline-based interpretation (BRCA1, p for trend=0.015; BRCA2, p=0.001). Our approach reduced the proportion of VUS from 19% (154/810) to 8.9% (72/810) in the retrospective validation data set. CONCLUSION: The classification in this study would minimise the 'uncertainty' in clinical interpretation, and this validated multifactorial model can be used for the reliable annotation of BRCA1/2 VUSs.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Feminino , Estudos de Associação Genética/métodos , Testes Genéticos , Humanos , Análise Multivariada , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Probabilidade , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , República da Coreia/epidemiologia
12.
Muscle Nerve ; 55(5): 727-734, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27593222

RESUMO

INTRODUCTION: Duchenne and Becker muscular dystrophies (DMD and BMD) are allelic X-linked recessive muscle diseases caused by mutations in the large and complex dystrophin gene. METHODS: We analyzed the dystrophin gene in 507 Korean DMD/BMD patients by multiple ligation-dependent probe amplification and direct sequencing. RESULTS: Overall, 117 different deletions, 48 duplications, and 90 pathogenic sequence variations, including 30 novel variations, were identified. Deletions and duplications accounted for 65.4% and 13.3% of Korean dystrophinopathy, respectively, suggesting that the incidence of large rearrangements in dystrophin is similar among different ethnic groups. We also detected sequence variations in >100 probands. The small variations were dispersed across the whole gene, and 12.3% were nonsense mutations. CONCLUSIONS: Precise genetic characterization in patients with DMD/BMD is timely and important for implementing nationwide registration systems and future molecular therapeutic trials in Korea and globally. Muscle Nerve 55: 727-734, 2017.


Assuntos
Distrofina/genética , Distrofia Muscular de Duchenne/genética , Mutação , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Éxons , Humanos , Masculino , Polimorfismo Genético , República da Coreia , Deleção de Sequência , Adulto Jovem
16.
Clin Chem Lab Med ; 54(7): 1157-60, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26587743

RESUMO

BACKGROUND: Quantifying the BCR-ABL1 rearrangement is important for monitoring chronic myelogenous leukemia (CML). To standardize BCR-ABL1 quantification, the World Health Organization (WHO) established the first international genetic reference panel. Here, we compared the BCR-ABL1 levels determined using international scale (IS)-based commercially available assays. METHODS: BCR-ABL1 transcripts were quantified using two IS-based assays. 10-1, 10-2, 10-3, 10-4, 10-5 and 10-6 dilutions of the b3a2 positive RNA were used for evaluating linearity, precision, and limit of detection. Correlation of the assay was evaluated by using DNA obtained from CML patients carrying the BCR-ABL1 b3a2 and b2a2 types. RESULTS: Both Ipsogen and Asuragen assays showed fine linearity with reasonable %CV. LOD of each assay was calculated as 0.003% for Ipsogen, and 0.005% for Asuragen. By comparing the results that were lower than 10% by either one of the assay, Ipsogen and Asuragen results showed an overall good linear correlation with a tendency for the Ipsogen assay to show slightly higher levels than the Asuragen assay for b3a2 transcript. For b2a2, the tendency was opposite, with Asuragen showing higher values than the Ipsogen. CONCLUSIONS: Two commercially available IS-based BCR-ABL1 assays showed an overall good quantitative correlation. It should be taken into consideration that each assay tended to produce higher values than the other, depending on the BCR-ABL1 subtypes, suggesting that a separate conversion factor for each subtype can be more helpful when BCR-ABL1 transcript levels are converted into IS.


Assuntos
Bioensaio/normas , Proteínas de Fusão bcr-abl/genética , Testes Genéticos/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Padrões de Referência , Bioensaio/métodos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença
18.
Breast Cancer Res Treat ; 146(1): 63-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24894343

RESUMO

Triple-negative breast cancer (TNBC) accounts for 12-24 % of all breast cancers. Here, we studied 221 familial breast and/or ovarian cancer patients from 37 hospitals using a comprehensive approach to identify large genomic rearrangements (LGRs) as well as sequence variants, and investigated the association between BRCA1/2 mutational status and TNBC. We performed direct sequencing or mutation scanning followed by direct sequencing. Then, 143 BRCA1/2 mutation-negative patients were screened for LGRs. In this study, the prevalence of BRCA1/2 mutations was high (36.9 %). The prevalence of BRCA1 mutations was similar to that of BRCA2 mutations: 49.4 versus 50.6 %, respectively. TNBC was diagnosed in 35.2 % of BRCA1/2 mutation carriers and 57.1 % of BRCA1 mutation carriers. Conversely, two-thirds of TNBC patients carried BRCA1/2 mutation(s), and about half were BRCA1 mutation carriers. When stratified by the mutated gene, TNBC prevalence in BRCA1 mutation carriers was significantly lower when there was a family history of ovarian cancer. Our multinomial logistic regression model demonstrated that no single factor was sufficient, and at least two factors, such as a patient with family history of both breast cancer and ovarian cancer or a patient diagnosed at a relatively young age (<40 years) with a TNBC phenotype, are necessary to indicate BRCA1/2 genetic testing in this population. Our results suggest that TNBC is a strong predictor for the presence of a BRCA1 mutation in this population, but additional risk factors should also be evaluated to ascertain a 10 % or higher prior probability of BRCA1/2 mutation testing.


Assuntos
Genes BRCA1 , Genes BRCA2 , Mutação , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idade de Início , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Prevalência , Prognóstico , República da Coreia/epidemiologia , Fatores de Risco , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia , Adulto Jovem
19.
BMC Cancer ; 14: 645, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25176351

RESUMO

BACKGROUND: Large genomic rearrangements (LGRs) in the BRCA1/2 genes are frequently observed in breast cancer patients who are negative for BRCA1/2 small mutations. Here, we examined 221 familial breast cancer patients from 37 hospitals to estimate the contribution of LGRs, in a nationwide context, to the development of breast cancer. METHODS: Direct sequencing or mutation scanning followed by direct sequencing was performed to screen small mutations. BRCA1/2 small mutation-negative patients were screened for the presence of LGRs using a multiple ligation-dependent probe amplification (MLPA) assay. RESULTS: Using a combined strategy to detect the presence of small mutations and LGRs, we identified BRCA1/2 small mutations in 78 (35.3%) out of 221 familial breast cancer patients and BRCA1 LGRs in 3 (2.1%) out of 143 BRCA1/2 small mutation-negative patients: the deletion of exons 11-13, the deletion of exons 13-15, and whole gene deletion of exons 1-24. The novel deletion of exons 11-13 is thought to result from a non-homologous recombination event mediated by a microhomology sequence comprised of 3 or 4 base pairs: c.3416_4357 + 1863delins187 (NG_005905.2: g.33369_44944delins187). CONCLUSIONS: In this study, we showed that LGRs were found in 3.7% (3/81) of the patients who had mutations in BRCA1 or BRCA2, and 7.5% (3/40) of patients with mutations in BRCA1. This suggests that the contribution of LGRs to familial breast cancer in this population might be comparable to that in other ethnic populations. Given these findings, an MLPA to screen for mutations in the BRCA1 gene is recommended as an initial screening test in highly selective settings.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ovarianas/genética , Adulto , Povo Asiático/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Análise Mutacional de DNA , Éxons , Feminino , Deleção de Genes , Humanos , Mutação , Neoplasias Ovarianas/sangue , Análise de Sequência de DNA
20.
Eur J Hum Genet ; 31(10): 1147-1153, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37414863

RESUMO

The Korean Genetic Diagnosis Program for Rare Disease (KGDP) enrolled 1890 patients with rare diseases between March 2017 and October 2022. Children and adolescents accounted for the majority of the patients, and systemic disease was the most common presenting symptom. The exome-based virtual disease-specific multigene panel was the most frequently used analytical method, with an overall diagnostic yield of 33.3%. A total of 629 positive cases were diagnosed, involving 297 genes. All 297 genes identified in these cases were confirmed to be known genes listed in the OMIM database. The nationwide KGDP network and its cooperation with the Korean Undiagnosed Diseases Program (KUDP) provide a more comprehensive genetic analysis of undiagnosed cases. The partnership between the KGDP and KUDP has the potential to improve the diagnosis and treatment options for patients. In conclusion, KGDP serves as the primary access point or gateway to KUDP.


Assuntos
Povo Asiático , Doenças Raras , Adolescente , Criança , Humanos , Povo Asiático/etnologia , Povo Asiático/genética , Bases de Dados Factuais , Exoma , Doenças Raras/diagnóstico , Doenças Raras/genética , República da Coreia
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