scholarly journals Investigation of Genetic Alterations in Congenital Heart Diseases in Prenatal Period

2021 ◽  
Author(s):  
Emine Ikbal Atli ◽  
Engin Atli ◽  
Sinem Yalcintepe ◽  
Selma Demir ◽  
Rasime Kalkan ◽  
...  
Keyword(s):  
Congenital Heart ◽  
Chromosomal Abnormalities ◽  
Single Nucleotide Polymorphism Array ◽  
Heart Diseases ◽  
Genetic Alterations ◽  
Chromosomal Microarray ◽  
Single Nucleotide ◽  
Dna Mutation ◽  
Genetic Examination ◽  
Direct Sequence Analysis

AbstractThe prenatal diagnosis of congenital heart disease (CHD) is important because of mortality risk. The onset of CHD varies, and depending on the malformation type, the risk of aneuploidy is changed. To identify possible genetic alterations in CHD, G-banding, chromosomal microarray or if needed DNA mutation analysis and direct sequence analysis should be planned.In present study, to identify genetic alterations, cell culture, karyotype analysis, and single nucleotide polymorphism, array analyses were conducted on a total 950 samples. Interventional prenatal genetic examination was performed on 23 (2, 4%, 23/950) fetal CHD cases. Chromosomal abnormalities were detected in 5 out of 23 cases (21, 7%). Detected chromosomal abnormalities were 10q23.2 deletion, trisomy 18, 8p22.3-p23.2 deletion, 8q21.3-q24.3 duplication, 11q24.2q24.5 (9 Mb) deletion, and 8p22p12 (16.8 Mb) deletion. Our study highlights the importance of genetic testing in CHD.

scholarly journals Neuroblastoma with flat genomic profile: a question of representativity?

2018 ◽  
pp. bcr-2018-225568
Author(s):  
Anders Valind ◽  
Ingrid Öra ◽  
Fredrik Mertens ◽  
David Gisselsson
Keyword(s):  
Single Nucleotide Polymorphism Array ◽  
Reference Sample ◽  
Genetic Alterations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide Variants ◽  
Array Analysis ◽  
Allelic Profile ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Genome Copy Number

Neuroblastoma is one of the most common paediatric malignancies. Detection of somatic genetic alterations in this tumour is instrumental for its risk stratification and treatment. On the other hand, an absence of detected chromosomal imbalances in neuroblastoma biopsies is difficult to interpret because it is unclear whether this situation truly reflects the tumour genome or if it is due to suboptimal sampling. We here present a neuroblastoma in the left adrenal of a newborn. The tumour was subjected to single-nucleotide polymorphism array analysis of five tumour regions with >80% tumour cells in histological mirror sections. This revealed no aberrations compared with a normal reference sample from the patient. Whole exome sequencing identified two single-nucleotide variants present in most tumour regions, corroborating that the tumour resulted from monoclonal expansion. Our data provide proof-of-principle that rare cases of neuroblastoma can have a normal whole genome copy number and allelic profile.

scholarly journals WT1 mutations in T-ALL

Blood ◽  
2009 ◽  
Vol 114 (5) ◽  
pp. 1038-1045 ◽  
Author(s):  
Valeria Tosello ◽  
Marc R. Mansour ◽  
Kelly Barnes ◽  
Maddalena Paganin ◽  
Maria Luisa Sulis ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Single Nucleotide Polymorphism Array ◽  
Lymphoblastic Leukemia ◽  
Suppressor Gene ◽  
Genetic Alterations ◽  
Array Analysis ◽  
Single Nucleotide ◽  
Chromosomal Markers ◽  
Cell Acute Lymphoblastic Leukemia

The molecular mechanisms involved in disease progression and relapse in T-cell acute lymphoblastic leukemia (T-ALL) are poorly understood. We used single nucleotide polymorphism array analysis to analyze paired diagnostic and relapsed T-ALL samples to identify recurrent genetic alterations in T-ALL. This analysis showed that diagnosis and relapsed cases have common genetic alterations, but also that relapsed samples frequently lose chromosomal markers present at diagnosis, suggesting that relapsed T-ALL emerges from an ancestral clone different from the major leukemic population at diagnosis. In addition, we identified deletions and associated mutations in the WT1 tumor suppressor gene in 2 of 9 samples. Subsequent analysis showed WT1 mutations in 28 of 211 (13.2%) of pediatric and 10 of 85 (11.7%) of adult T-ALL cases. WT1 mutations present in T-ALL are predominantly heterozygous frameshift mutations resulting in truncation of the C-terminal zinc finger domains of this transcription factor. WT1 mutations are most prominently found in T-ALL cases with aberrant rearrangements of the oncogenic TLX1, TLX3, and HOXA transcription factor oncogenes. Survival analysis demonstrated that WT1 mutations do not confer adverse prognosis in pediatric and adult T-ALL. Overall, these results identify the presence of WT1 mutations as a recurrent genetic alteration in T-ALL.

scholarly journals Differential Expression and Interaction network construction of Noncoding RNA and mRNA in Heart Tissue associated with Tetralogy of Fallot

2020 ◽  
Author(s):  
Hongdan Wang ◽  
Cunying Cui ◽  
Yanan Li ◽  
Yuanyuan Liu ◽  
Taibing Fan ◽  
...  
Keyword(s):  
Tetralogy Of Fallot ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Congenital Heart ◽  
Chromosomal Abnormalities ◽  
Heart Diseases ◽  
Right Ventricular Outflow Tract ◽  
Interaction Network ◽  
Tissue Samples ◽  
Non Coding Rna

ABSTRACTTetralogy of Fallot (TOF) is still the most common and complicated cyanotic congenital heart defect of all congenital heart diseases with a 10% incidence. Surgery repair is often necessary in infancy. The etiology of TOF is complex and genetic and epigenetic mechanisms such as chromosomal abnormalities, gene mutations, nucleic acid modifications, non-coding RNA, and circular RNA(circRNA) play an important role in its occurrence. RNA not only plays an auxiliary role of genetic information carrier, but also plays a more important role in various regulatory functions. There are few studies on the action mechanism of non-coding RNA. Aim to gain more in-depth knowledge of TOF, we collected tissue samples of the right ventricular outflow tract of 5 TOF children with no other intracardiac and extracardiac malformations and 5 normal fetuses. We systematically analyzed the specific long non-coding RNA (lncRNA), microRNA(miRNA), circRNA and messenger RNA(mRNA) profiles of TOF. To our knowledge, there are no reports of genome-wide study of transcriptome in TOF and we first obtained meaningful differentially expressed lncRNAs, miRNAs, circle RNA and mRNAs.

GATA4 Deletions Associated with Congenital Heart Diseases in South Brazil

2020 ◽  
Author(s):  
Maiara A. Floriani ◽  
Andressa B. Glaeser ◽  
Luiza E. Dorfman ◽  
Grasiela Agnes ◽  
Rafael F. M. Rosa ◽  
...  
Keyword(s):  
Congenital Heart ◽  
Chromosomal Abnormalities ◽  
Cardiac Development ◽  
Chromosome Region ◽  
Heart Diseases ◽  
Superior Vena ◽  
Copy Number Variants ◽  
Vena Cava ◽  
First Time ◽  
Dependent Probe

AbstractThe normal development of the heart comprises a highly regulated machinery of genetic events, involving transcriptional factors. Congenital heart disease (CHD), have been associated with chromosomal abnormalities and copy number variants (CNVs). Our goal was to investigate through the multiplex ligation-dependent probe amplification (MLPA) technique, the presence of CNVs in reference genes for normal cardiac development in patients with CHD. GATA4, NKX2–5, TBX5, BMP4, and CRELD1 genes and 22q11.2 chromosome region were analyzed in 207 children with CHD admitted for the first time in a cardiac intensive care unit from a pediatric hospital. CNVs were detected in seven patients (3.4%): four had a 22q11.2 deletion (22q11DS) (1.9%), two had a GATA4 deletion (1%) and one had a 22q11.2 duplication (0.5%). No patients with CNVs in the NKX2–5, TBX5, BMP4, and CRELD1 genes were identified. GATA4 deletions appear to be present in a significant number of CHD patients, especially those with septal defects, persistent left superior vena cava, pulmonary artery abnormalities, and extracardiac findings. GATA4 screening seems to be more effective when directed to these CHDs. The investigation of CNVs in GATA4 and 22q11 chromosome region in patients with CHD is important to anticipating the diagnosis, and to contributing to family planning.

Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome

2016 ◽  
Vol 70 (5) ◽  
pp. 435-442 ◽  
Author(s):  
Fernanda Borges da Silva ◽  
João Agostinho Machado-Neto ◽  
Virginia Helena Leira Lipoli Bertini ◽  
Elvira Deolinda Rodrigues Pereira Velloso ◽  
Cristina Alonso Ratis ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Myelodysplastic Syndrome ◽  
Chromosomal Abnormalities ◽  
Single Nucleotide Polymorphism Array ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

scholarly journals Utility of Whole-Exome Sequencing in Pediatric and Medical Diagnosis

2020 ◽  
Author(s):  
Mohd Fareed ◽  
Varun Sharma ◽  
Hemender Singh
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Symptoms ◽  
Heart Diseases ◽  
Genetic Disorders ◽  
Single Gene ◽  
Genetic Alterations ◽  
Child Growth ◽  
Chromosomal Microarray ◽  
Whole Exome

Genetic disorders are preeminent determinants of infant mortality. The inherited pediatric-onset genetic disorders have consequential stress on child growth and development: several congenital, complex and rare disorders with indistinguishable clinical symptoms where diagnosis always remains a challenging task. Traditional diagnosis methods include biochemical tests followed by chromosomal microarray and sequencing of a single gene or panel of genes. These methods had several limitations, but with the advent of whole-exome sequencing (WES), genetic testing has become cost-effective and transformative. Exome sequencing has been known for its effectiveness, which appropriately elucidates and distinguishes the heterogeneous disorders to avoid misdiagnosis and decode the underlying genetic alterations. WES has led to discovering genes and genomic variants in a broad spectrum of diseases, including autism, epilepsy, congenital heart diseases, neurodevelopmental diseases, cancer, nephrotic disorders, neural tube defects and fetal structural anomalies. WES is significant in producing immense genomic biomarkers that can be made as appropriate pharmacogenomic targets for drug therapy. In this article, we analyze the recent exploration of WES technology to revolutionize not only the process of genetic variation and disease detection but also the convention of preventative and targeted drug discovery.

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