Whole exome sequencing is necessary to clarify ID/DD cases with de novo copy number variants of uncertain significance: Two proof-of-concept examples

2016 ◽  
Vol 170 (7) ◽  
pp. 1772-1779 ◽  
Author(s):  
Elisa Giorgio ◽  
Andrea Ciolfi ◽  
Elisa Biamino ◽  
Viviana Caputo ◽  
Eleonora Di Gregorio ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Proof Of Concept ◽  
Variants Of Uncertain Significance ◽  
Whole Exome ◽  
Uncertain Significance

scholarly journals Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy

2021 ◽  
Vol 14 ◽  
Author(s):  
Tiejia Jiang ◽  
Jia Gao ◽  
Lihua Jiang ◽  
Lu Xu ◽  
Congying Zhao ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Pediatric Patients ◽  
De Novo ◽  
Treatment Options ◽  
Copy Number Variants ◽  
Genetic Diagnosis ◽  
Single Nucleotide Variants ◽  
Whole Exome

Epilepsy is one of the most common neurological disorders in pediatric patients with other underlying neurological defects. Identifying the underlying etiology is crucial for better management of the disorder. We performed trio-whole exome sequencing in 221 pediatric patients with epilepsy. Probands were divided into seizures with developmental delay/intellectual disability (DD/ID) and seizures without DD/ID groups. Pathogenic (P) or likely pathogenic (LP) variants were identified in 71/110 (64.5%) patients in the seizures with DD/ID group and 21/111 (18.9%) patients in the seizures without DD/ID group (P < 0.001). Eighty-seven distinct P/LP single nucleotide variants (SNVs)/insertion deletions (Indels) were detected, with 55.2% (48/87) of them being novel. All aneuploidy and P/LP copy number variants (CNVs) larger than 100 Kb were identifiable by both whole-exome sequencing and copy number variation sequencing (CNVseq) in 123 of individuals (41 pedigrees). Ten of P/LP CNVs in nine patients and one aneuploidy variant in one patient (Patient #56, #47, XXY) were identified by CNVseq. Herein, we identified seven genes (NCL, SEPHS2, PA2G4, SLC35G2, MYO1C, GPR158, and POU3F1) with de novo variants but unknown pathogenicity that were not previously associated with epilepsy. Potential effective treatment options were available for 32 patients with a P/LP variant, based on the molecular diagnosis. Genetic testing may help identify the molecular etiology of early onset epilepsy and DD/ID and further aid to choose the appropriate treatment strategy for patients.

scholarly journals RefCNV: Identification of Gene-Based Copy Number Variants Using Whole Exome Sequencing

2016 ◽  
Vol 15 ◽  
pp. CIN.S36612 ◽  
Author(s):  
Lun-Ching Chang ◽  
Biswajit Das ◽  
Chih-Jian Lih ◽  
Han Si ◽  
Corinne E. Camalier ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Estimation Methods ◽  
Single Nucleotide Variants ◽  
False Positive Error ◽  
Reference Set ◽  
Genome Wide ◽  
Whole Exome

With rapid advances in DNA sequencing technologies, whole exome sequencing (WES) has become a popular approach for detecting somatic mutations in oncology studies. The initial intent of WES was to characterize single nucleotide variants, but it was observed that the number of sequencing reads that mapped to a genomic region correlated with the DNA copy number variants (CNVs). We propose a method RefCNV that uses a reference set to estimate the distribution of the coverage for each exon. The construction of the reference set includes an evaluation of the sources of variability in the coverage distribution. We observed that the processing steps had an impact on the coverage distribution. For each exon, we compared the observed coverage with the expected normal coverage. Thresholds for determining CNVs were selected to control the false-positive error rate. RefCNV prediction correlated significantly ( r = 0.96–0.86) with CNV measured by digital polymerase chain reaction for MET (7q31), EGFR (7p12), or ERBB2 (17q12) in 13 tumor cell lines. The genome-wide CNV analysis showed a good overall correlation (Spearman's coefficient = 0.82) between RefCNV estimation and publicly available CNV data in Cancer Cell Line Encyclopedia. RefCNV also showed better performance than three other CNV estimation methods in genome-wide CNV analysis.

scholarly journals Application of Whole-Exome Sequencing in Detecting Copy Number Variants in Patients with Developmental Delay and/or Multiple Congenital Malformations

2020 ◽  
Vol 22 (8) ◽  
pp. 1041-1049
Author(s):  
Évelin A. Zanardo ◽  
Fabíola P. Monteiro ◽  
Samar N. Chehimi ◽  
Yanca G. Oliveira ◽  
Alexandre T. Dias ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Developmental Delay ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Congenital Malformations ◽  
Copy Number Variants ◽  
Whole Exome

Detection of Clinically Relevant Copy Number Variants with Whole-Exome Sequencing

2013 ◽  
Vol 34 (10) ◽  
pp. 1439-1448 ◽  
Author(s):  
Joep de Ligt ◽  
Philip M. Boone ◽  
Rolph Pfundt ◽  
Lisenka E.L.M. Vissers ◽  
Todd Richmond ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Whole Exome

scholarly journals CANOES: detecting rare copy number variants from whole exome sequencing data

2014 ◽  
Vol 42 (12) ◽  
pp. e97-e97 ◽  
Author(s):  
Daniel Backenroth ◽  
Jason Homsy ◽  
Laura R. Murillo ◽  
Joe Glessner ◽  
Edwin Lin ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Sequencing Data ◽  
Exome Sequencing Data ◽  
Whole Exome ◽  
Whole Exome Sequencing Data

scholarly journals Platform comparison of detecting copy number variants with microarrays and whole-exome sequencing

Genomics Data ◽  
2014 ◽  
Vol 2 ◽  
pp. 144-146 ◽  
Author(s):  
Joep de Ligt ◽  
Philip M. Boone ◽  
Rolph Pfundt ◽  
Lisenka E.L.M. Vissers ◽  
Nicole de Leeuw ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Whole Exome ◽  
Platform Comparison

scholarly journals EXCAVATOR: detecting copy number variants from whole-exome sequencing data

2013 ◽  
Vol 14 (10) ◽  
pp. R120 ◽  
Author(s):  
Alberto Magi ◽  
Lorenzo Tattini ◽  
Ingrid Cifola ◽  
Romina D’Aurizio ◽  
Matteo Benelli ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Sequencing Data ◽  
Exome Sequencing Data ◽  
Whole Exome ◽  
Whole Exome Sequencing Data

scholarly journals Application of whole‐exome sequencing for detecting copy number variants in CMT1A/HNPP

2016 ◽  
Vol 90 (2) ◽  
pp. 177-181 ◽  
Author(s):  
H.‐Y. Jo ◽  
M.‐H. Park ◽  
H.‐M. Woo ◽  
M.H. Han ◽  
B.‐Y. Kim ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Whole Exome

scholarly journals Enhanced copy number variants detection from whole-exome sequencing data using EXCAVATOR2

2016 ◽  
pp. gkw695 ◽  
Author(s):  
Romina D'Aurizio ◽  
Tommaso Pippucci ◽  
Lorenzo Tattini ◽  
Betti Giusti ◽  
Marco Pellegrini ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Sequencing Data ◽  
Exome Sequencing Data ◽  
Whole Exome ◽  
Whole Exome Sequencing Data
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