scholarly journals Copy number variations of chromosome 17p11.2 region in children with development delay and in fetuses with abnormal imaging findings

2021 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Xiaoliang Liu ◽  
Haiming Gao ◽  
Rong He ◽  
Guoming Chu ◽  
...  
Keyword(s):  
Copy Number ◽  
Phenotypic Variability ◽  
Copy Number Variations ◽  
Congenital Defects ◽  
Genetic Characteristics ◽  
Development Delay ◽  
Chromosome Imbalance ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Dependent Probe

Abstract Background: Deletion and duplication of the -3.7 Mb region in 17p11.2 result in two reciprocal syndromes, Smith-Magenis syndrome and Potocki-Lupski syndrome, which are well-known development disorders. The purpose of this study is to identify the prevalence, genetic characteristics and clinical phenotype of 17p11.2 deletion/duplication in Chinese children with development delay and in fetuses with potential congenital defects.Methods: 7077 children with development delay and/or intellectual disability were screened by multiplex ligation-dependent probe amplification (MLPA) P245 assay. 7319 fetuses with potential congenital defects were detected using next generation sequencing (NGS) technique.Results: 417 of 7077 children patients were identified to carry chromosome imbalance. Among them, 28 (28/7077, 0.4 %) cases had imbalance at chromosome 17p11.2, of which 12 cases (42.9 %) had heterozygous deletions and 16 (57.1 %) had heterogeneous duplications. The phenotypes of these 28 children were variable, including neurobehavioral disorders, craniofacial/skeletal anomalies, immunologic defects, ocular problems, and organ malformations. 263 of 7319 fetuses were recognized to have genomic copy number variations (CNV). Only 2 of them were found to harbor 17p11.2 imbalance. The fetus with deletion presented with ventricular septal defect and the fetus with reciprocal duplication had cerebral ventricle dilation.Conclusion: Our study highlights the phenotypic variability associated with 17p11.2 variations in China. The results further expand the phenotypic spectrum of SMS/PTLS and increase awareness of these disruptive mutations among clinicians.

scholarly journals Copy number variations of chromosome 17p11.2 region in children with development delay and in fetuses with abnormal imaging findings

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuanyuan Zhang ◽  
Xiaoliang Liu ◽  
Haiming Gao ◽  
Rong He ◽  
Guoming Chu ◽  
...  
Keyword(s):  
Copy Number ◽  
Phenotypic Variability ◽  
Copy Number Variations ◽  
Congenital Defects ◽  
Genetic Characteristics ◽  
Clinical Phenotypes ◽  
Development Delay ◽  
Chromosome Imbalance ◽  
Generation Sequencing ◽  
Dependent Probe

Abstract Background Deletion and duplication of the 3.7 Mb region in 17p11.2 result in two syndromes, Smith-Magenis syndrome and Potocki-Lupski syndrome, which are well-known development disorders. The purpose of this study was to determine the prevalence, genetic characteristics and clinical phenotypes of 17p11.2 deletion/duplication in Chinese children with development delay and in fetuses with potential congenital defects. Methods 7077 children with development delay and/or intellectual disability were screened by multiplex ligation-dependent probe amplification P245 assay. 7319 fetuses with potential congenital defects were tested using next generation sequencing technique. Results 417 of 7077 pediatric patients were determined to carry chromosome imbalance. 28 (28/7077, 0.4%) cases had imbalance at chromosome 17p11.2. Among them, 12 cases (42.9%) had heterozygous deletions and 16 cases (57.1%) had heterozygous duplications. The clinical phenotypes were variable, including neurobehavioral disorders, craniofacial/skeletal anomalies, immunologic defects, ocular problems and organ malformations. 263 of 7319 fetuses were recognized to have genomic copy number variations. Only 2 of them were found to harbor 17p11.2 imbalance. The fetus with deletion presented with ventricular septal defect and the fetus with duplication had cerebral ventricle dilation. Conclusion Our study highlights the phenotypic variability associated with 17p11.2 variations in China. The results further expand the phenotypic spectrum of SMS/PTLS and increase awareness of these disruptive mutations among clinicians.

scholarly journals Analysis of Copy Number Variations in Solid Tumors Using a Next Generation Sequencing Custom Panel

2021 ◽  
Vol 2 (2) ◽  
pp. 123-134
Author(s):  
Marta Vives-Usano ◽  
Beatriz García Pelaez ◽  
Ruth Román Lladó ◽  
Mónica Garzón Ibañez ◽  
Erika Aldeguer ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Copy Number ◽  
Copy Number Variations ◽  
Next Generation ◽  
Ffpe Samples ◽  
Custom Panel ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Approach Time ◽  
Selection Of

Somatic copy number variations (CNV; i.e., amplifications and deletions) have been implicated in the origin and development of multiple cancers and some of these aberrations are designated targets for therapies. Although FISH is still considered the gold standard for CNV detection, the increasing number of potentially druggable amplifications to be assessed makes a gene-by-gene approach time- and tissue-consuming. Here we investigated the potential of next generation sequencing (NGS) custom panels to simultaneously determine CNVs across FFPE solid tumor samples. DNA was purified from cell lines and FFPE samples and analyzed by NGS sequencing using a 20-gene custom panel in the GeneReader Platform®. CNVs were identified using an in-house algorithm based on the UMI read coverage. Retrospective validation of in-house algorithm to identify CNVs showed 97.1% concordance rate with the NGS custom panel. The prospective analysis was performed in a cohort of 243 FFPE samples from patients arriving at our hospital, which included 74 NSCLC tumors, 148 CRC tumors, and 21 other tumors. Of them, 33% presented CNVs by NGS and in 14 cases (5.9%) the CNV was the only alteration detected. We have identified CNV alterations in about one-third of our cohort, including FGFR1, CDK6, CDK4, EGFR, MET, ERBB2, BRAF, or KRAS. Our work highlights the need to include CNV testing as a part of routine NGS analysis in order to uncover clinically relevant gene amplifications that can guide the selection of therapies.

scholarly journals Copy number variations in female infertility in China

2019 ◽  
Vol 22 (1) ◽  
pp. 5-10
Author(s):  
W Huang ◽  
J Wang ◽  
M Pang ◽  
Q Zhao ◽  
L Kong ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variations ◽  
Female Infertility ◽  
Functional Genes ◽  
Chromosome X ◽  
Republic Of China ◽  
Number Variation ◽  
Next Generation Sequencing Ngs ◽  
The Relationship ◽  
Generation Sequencing

AbstractCopy number variation (CNV) is a main cause of male infertility, yet its influence still remains elusive in that of females. To investigate the correlation between CNV and female infertility, we applied whole-genome CNV analyses by next generation Sequencing (NGS), and analyzed 324 female infertility samples in Xinjiang Province, People's Republic of China. We identified 29 CNVs in total, of which 10 were novel CNVs. We found these CNVs mostly in chromosome X. The CNVs from one sample overlapped the POF1B gene that was related to premature ovarian failure (POF). The rest of these CNVs overlapped important functional genes related to neuropathy, brain, skin and retina, and the relationship between these CNVs and fertility needs to be studied further. We also found recurrent CNVs located on Xp22.31 and 22ql 1.21 in five and three cases, respectively. Our study first identified and characterized CNVs (CNVs preference, recurrent CNVs) in female infertility, also provided genetic evidence and references for future study and infertility etiology research.

scholarly journals The ICR96 exon CNV validation series: a resource for orthogonal assessment of exon CNV calling in NGS data

2017 ◽  
Vol 2 ◽  
pp. 35 ◽  
Author(s):  
Shazia Mahamdallie ◽  
Elise Ruark ◽  
Shawn Yost ◽  
Emma Ramsay ◽  
Imran Uddin ◽  
...  
Keyword(s):  
Sequencing Data ◽  
Targeted Next Generation Sequencing ◽  
Negative Results ◽  
Targeted Ngs ◽  
Predisposition Genes ◽  
Next Generation Sequencing Ngs ◽  
Ngs Data ◽  
Validation Series ◽  
Generation Sequencing ◽  
Dependent Probe

Detection of deletions and duplications of whole exons (exon CNVs) is a key requirement of genetic testing. Accurate detection of this variant type has proved very challenging in targeted next-generation sequencing (NGS) data, particularly if only a single exon is involved. Many different NGS exon CNV calling methods have been developed over the last five years. Such methods are usually evaluated using simulated and/or in-house data due to a lack of publicly-available datasets with orthogonally generated results. This hinders tool comparisons, transparency and reproducibility. To provide a community resource for assessment of exon CNV calling methods in targeted NGS data, we here present the ICR96 exon CNV validation series. The dataset includes high-quality sequencing data from a targeted NGS assay (the TruSight Cancer Panel) together with Multiplex Ligation-dependent Probe Amplification (MLPA) results for 96 independent samples. 66 samples contain at least one validated exon CNV and 30 samples have validated negative results for exon CNVs in 26 genes. The dataset includes 46 exon CNVs in BRCA1, BRCA2, TP53, MLH1, MSH2, MSH6, PMS2, EPCAM or PTEN, giving excellent representation of the cancer predisposition genes most frequently tested in clinical practice. Moreover, the validated exon CNVs include 25 single exon CNVs, the most difficult type of exon CNV to detect. The FASTQ files for the ICR96 exon CNV validation series can be accessed through the European-Genome phenome Archive (EGA) under the accession number EGAS00001002428.

scholarly journals Multiplex ligation-dependent probe amplification – a short overview

2020 ◽  
Vol 28 (2) ◽  
pp. 123-131
Author(s):  
Valeriu Moldovan ◽  
Elena Moldovan
Keyword(s):  
Copy Number ◽  
Genetic Disorders ◽  
Cost Effective ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Gene Deletions ◽  
Conventional Cytogenetic Analysis ◽  
Main Technique ◽  
Cost Effective Technique ◽  
Dependent Probe

AbstractMultiplex Ligation-dependent Probe Amplification is a technique proposed for the detection of deletions or duplications that may lead to copy number variations in genomic DNA, mainly due to its higher resolution, and shorter overall diagnosis time, when compared with techniques traditionally used, namely karyotyping, fluorescence in situ hybridization, and array comparative genomic hybridization. Multiplex Ligation-dependent Probe Amplification is a fast (about 2 days), useful and cost-effective technique, being suitable for the diagnosis of hereditary conditions caused by complete or partial gene deletions or duplications, as these conditions are either more difficult or impossible to be diagnosed by other techniques, such as PCR, Real-Time PCR, or sequencing (Sanger or Next Generation). Due to its numerous advantages over conventional cytogenetic analysis techniques, Multiplex Ligation-dependent Probe Amplification could be used in the near future as the main technique for the molecular investigation of genetic conditions caused by copy number variations, in both rare and complex genetic disorders.

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