Genomic Chaos (Multiple Copy Number Variations and Structural Reorganization) Detected in Two Prenatal Cases

2021 ◽  
pp. 1-7
Author(s):  
Elisabet Lloveras ◽  
Anna Canellas ◽  
Alberto Plaja ◽  
Laura Barranco ◽  
Daniel Fernández ◽  
...  
Keyword(s):  
Structural Variation ◽  
New Technologies ◽  
Copy Number Variations ◽  
Genomic Rearrangements ◽  
Chromosomal Microarray ◽  
Structural Reorganization ◽  
Catastrophic Event ◽  
Routine Diagnosis ◽  
Generation Sequencing ◽  
Complex Chromosome

The use of new technologies in the routine diagnosis of constitutional abnormalities, such as high-resolution chromosomal microarray and next-generation sequencing, has unmasked new mechanisms for generating structural variation of the human genome. For example, complex chromosome rearrangements can originate by a chromosome catastrophe phenomenon in which numerous genomic rearrangements are apparently acquired in a single catastrophic event. This phenomenon is named chromoanagenesis (from the Greek “chromo” for chromosome and “anagenesis” for rebirth). Herein, we report 2 cases of genomic chaos detected at prenatal diagnosis. The terms “chromothripsis” and “chromoanasynthesis” and the challenge of genetic counseling are discussed.

scholarly journals Design and Validation of a Gene-Targeted, Next-Generation Sequencing Panel for Routine Diagnosis in Gliomas

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 773 ◽  
Author(s):  
Nicky D’Haene ◽  
Bárbara Meléndez ◽  
Oriane Blanchard ◽  
Nancy De Nève ◽  
Laetitia Lebrun ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Simultaneous Detection ◽  
Growth Factor Receptor ◽  
Copy Number Variations ◽  
World Health ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Molecular Alterations ◽  
Routine Diagnosis ◽  
Generation Sequencing

The updated 2016 World Health Organization (WHO) classification system for gliomas integrates molecular alterations and histology to provide a greater diagnostic and prognostic utility than the previous, histology-based classification. The increasing number of markers that are tested in a correct diagnostic procedure makes gene-targeted, next-generation sequencing (NGS) a powerful tool in routine pathology practice. We designed a 14-gene NGS panel specifically aimed at the diagnosis of glioma, which allows simultaneous detection of mutations and copy number variations, including the 1p/19q-codeletion and Epidermal Growth Factor Receptor (EGFR) amplification. To validate this panel, we used reference mutated DNAs, nontumor and non-glioma samples, and 52 glioma samples that were previously characterized. The panel was then prospectively applied to 91 brain lesions. A specificity of 100% and sensitivity of 99.4% was achieved for mutation detection. Orthogonal methods, such as in situ hybridization and immunohistochemical techniques, were used for validation, which showed high concordance. The molecular alterations that were identified allowed diagnosis according to the updated WHO criteria, and helped in the differential diagnosis of difficult cases. This NGS panel is an accurate and sensitive method, which could replace multiple tests for the same sample. Moreover, it is a rapid and cost-effective approach that can be easily implemented in the routine diagnosis of gliomas.

scholarly journals Integrated CNV-seq, karyotyping and SNP-array analyses for effective prenatal diagnosis of chromosomal mosaicism

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Na Ma ◽  
Hui Xi ◽  
Jing Chen ◽  
Ying Peng ◽  
Zhengjun Jia ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Sex Chromosome ◽  
Snp Array ◽  
Genomic Rearrangements ◽  
Chromosomal Mosaicism ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Low Level ◽  
Autosomal Aneuploidy ◽  
Number Variation

Abstract Background Emerging studies suggest that low‐coverage massively parallel copy number variation sequencing (CNV-seq) more sensitive than chromosomal microarray analysis (CMA) for detecting low-level mosaicism. However, a retrospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of CNV-seq compared with CMA is warranted. Methods A total of 72 mosaicism cases identified by karyotyping or CMA were recruited to the study. There were 67 mosaic samples co-analysed by CMA and CNV-seq, comprising 40 with sex chromosome aneuploidy, 22 with autosomal aneuploidy and 5 with large cryptic genomic rearrangements. Results Of the 67 positive mosaic cases, the levels of mosaicism defined by CNV-seq ranged from 6 to 92% compared to the ratio from 3 to 90% by karyotyping and 20% to 72% by CMA. CNV-seq not only identified all 43 chromosomal aneuploidies or large cryptic genomic rearrangements detected by CMA, but also provided a 34.88% (15/43) increased yield compared with CMA. The improved yield of mosaicism detection by CNV-seq was largely due to the ability to detect low level mosaicism below 20%. Conclusion In the context of prenatal diagnosis, CNV-seq identified additional and clinically significant mosaicism with enhanced resolution and increased sensitivity. This study provides strong evidence for applying CNV-seq as an alternative to CMA for detection of aneuploidy and mosaic variants.

(4) Routine diagnosis of familial hypercholesterolemia with next generation sequencing

2012 ◽  
Vol 223 (2) ◽  
pp. 528-529
Author(s):  
L. Palacios ◽  
E. Olano-Martin ◽  
S. Catarino ◽  
N. Aizpuru ◽  
A. Martinez ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Familial Hypercholesterolemia ◽  
Next Generation ◽  
Routine Diagnosis ◽  
Generation Sequencing
Sign in / Sign up

Export Citation Format

Share Document