scholarly journals Clinical and molecular diagnostic study of 320 Chinese children with epilepsy by Genome Sequencing

2020 ◽  
Author(s):  
Dongfang Zou ◽  
Lin Wang ◽  
Jianxiang Liao ◽  
Hongdou Xiao ◽  
Jing Duan ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Copy Number ◽  
Copy Number Variant ◽  
Chinese Children ◽  
Deletion Syndrome ◽  
Molecular Diagnostic ◽  
Chromosomal Microarray Analysis ◽  
Diagnostic Study ◽  
Single Nucleotide ◽  
First Choice

Purpose: To evaluate the diagnostic value of Genome Sequencing(GS) in children with epilepsy. Methods: We performed GS on 320 Chinese children with epilepsy and interpreted Single Nucleotide Variants (SNVs) and Copy Number Variant (CNVs) of all samples. The complete pedigree and clinical data of the probands were established and followed up. The clinical phenotypes, treatments, prognoses and genotypes of the patients were analyzed. Results: Pathogenic/likely pathogenic variants were found in 122 of 320 children (38.13%), of whom, 92 (28.8%) had SNVs, 27 (8.4%) had CNVs, and three had both SNVs and CNVs. Among these variants, there were 3 CNVs of <100K in length. The most frequently mutated gene was SCN1A (10.9%,10/92), which is related to Dravet Syndrome, followed by PRRT2 (8.7%,8/92), which is relevant to benign familial infantile epilepsy, TSC2 (7.6%,7/92), which is associated with Tuberous Sclerosis. The most common recurrent CNVs were 17p13.3 deletion (18.5%, 5/27), 16p11.2 deletion syndrome (14.8%, 4/27), 15q11.2 deletion (11.1%, 3/27), which are related to epilepsy, developmental retardation and congenital abnormalities. The diagnostic yield was higher as the age of seizure onset was smaller. The highest detection rate was 75% in whom developed seizures within one month after birth. 13.4% (43/320) cases were identified to be treatable based on GS. 1% (3/320) of epilepsy patients received direct therapeutic measures and demonstrated favorable prognosis. Conclusion: GS can complete the genetic diagnosis, individualized treatment, and family reproductive guidance for patients. GS can replace Exome Sequencing and Chromosomal Microarray Analysis and is expected to be the first choice of genetic testing method for patients with epilepsy. Key Words: epilepsy; Genome Sequencing; Copy Number Variant; seizure; Single Nucleotide Variations

scholarly journals Peruvian Newborn Male with 3p13 Deletion Syndrome Encompassing the FOXP1 Gene: Review of the Literature

2020 ◽  
Vol 09 (04) ◽  
pp. 270-278
Author(s):  
Hugo H. Abarca-Barriga ◽  
Milana Trubnykova ◽  
Félix Chavesta-Velásquez ◽  
Claudia Barletta-Carrillo ◽  
Marco Ordoñez-Linares ◽  
...  
Keyword(s):  
Copy Number ◽  
Choanal Atresia ◽  
Copy Number Variant ◽  
Autism Spectrum ◽  
Deletion Syndrome ◽  
Chromosomal Microarray ◽  
Facial Dysmorphism ◽  
Chromosomal Microarray Analysis ◽  
Heart Malformation ◽  
Number Variation

AbstractCopy number variation in loss of 3p13 is an infrequently reported entity characterized by hypertelorism, aniridia, microphthalmia, high palate, neurosensorial deafness, camptodactyly, heart malformation, development delay, autism spectrum disorder, seizures, and choanal atresia. The entity is caused probably by haploinsufficiency for FOXP1, UBA3, FAM19A1, and MITF. We report a newborn male with hypotonia, facial dysmorphism, heart malformation, and without clinical diagnosis; nevertheless, the use of appropriate genetic test, such us the chromosomal microarray analysis allowed identification of a copy number variant in loss of 5.5 Mb at chromosome 3 (p13-p14.1), that included 54 genes, encompassing FOXP1 gene. We compare the findings in our Peruvian patient to those of earlier reported patients; furthermore, add new signs for this entity.

scholarly journals Detection and characterization of copy number variants based on whole-genome sequencing by DNBSEQ platforms

2019 ◽  
Author(s):  
Junhua Rao ◽  
Lihua Peng ◽  
Fang Chen ◽  
Hui Jiang ◽  
Chunyu Geng ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Copy Number Variant ◽  
Whole Genome ◽  
Genome Wide ◽  
Wide Range ◽  
Distribution Sensitivity ◽  
Cnv Detection

AbstractBackgroundNext-generation sequence (NGS) has rapidly developed in past years which makes whole-genome sequencing (WGS) becoming a more cost- and time-efficient choice in wide range of biological researches. We usually focus on some variant detection via WGS data, such as detection of single nucleotide polymorphism (SNP), insertion and deletion (Indel) and copy number variant (CNV), which playing an important role in many human diseases. However, the feasibility of CNV detection based on WGS by DNBSEQ™ platforms was unclear. We systematically analysed the genome-wide CNV detection power of DNBSEQ™ platforms and Illumina platforms on NA12878 with five commonly used tools, respectively.ResultsDNBSEQ™ platforms showed stable ability to detect slighter more CNVs on genome-wide (average 1.24-fold than Illumina platforms). Then, CNVs based on DNBSEQ™ platforms and Illumina platforms were evaluated with two public benchmarks of NA12878, respectively. DNBSEQ™ and Illumina platforms showed similar sensitivities and precisions on both two benchmarks. Further, the difference between tools for CNV detection was analyzed, and indicated the selection of tool for CNV detection could affected the CNV performance, such as count, distribution, sensitivity and precision.ConclusionThe major contribution of this paper is providing a comprehensive guide for CNV detection based on WGS by DNBSEQ™ platforms for the first time.

scholarly journals JAX-CNV: A whole genome sequencing-based algorithm for copy number detection at clinical grade level

2021 ◽  
Author(s):  
Wan-Ping Lee ◽  
Qihui Zhu ◽  
Xiaofei Yang ◽  
Silvia Liu ◽  
Eliza Cerveira ◽  
...  
Keyword(s):  
False Discovery Rate ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Copy Number Variant ◽  
Fold Increase ◽  
Chromosomal Microarray ◽  
Whole Genome ◽  
False Discovery ◽  
Calling Algorithm

We aimed to develop a whole genome sequencing (WGS)-based copy number variant (CNV) calling algorithm with the potential of replacing chromosomal microarray assay (CMA) for clinical diagnosis. JAX-CNV is thus developed for CNV detection from WGS. The performance of this CNV calling algorithm was evaluated in a blinded manner on 31 samples and compared to the results of clinically-validated CMAs. Comparing to 112 CNVs reported by clinically-validated CMAs of the 31 samples, JAX-CNV is 100% recalling them. Besides, JAX-CNV identified an average of 30 CNVs per individual that is an approximately seven-fold increase compared to calls of clinically-validated CMAs. Experimental validation of 24 randomly selected CNVs, showed one false positive (i.e., a false discovery rate of 4.17%). A robustness test on lower-coverage data revealed a 100% sensitivity for CNVs greater than 300 kb (the current threshold for College of American Pathologists) down to 10x coverage. For CNVs greater than 50 kb, sensitivities were 100% for coverages deeper than 20x, 97% for 15x, and 95% for 10x. We developed a WGS-based CNV pipeline, including this newly developed CNV caller JAX-CNV, and found it capable of detecting CMA reported CNVs at 100% sensitivity with about 4% false discovery rate. We propose that JAX-CNV could be further examined in a multi-institutional study to justify the transition of first-tier genetic testing from CMAs to WGS. JAX-CNV is available on https://github.com/TheJacksonLaboratory/JAX-CNV.

scholarly journals Prenatal Diagnosis of 17p11.2 Copy Number Abnormalities Associated With Smith–Magenis and Potocki–Lupski Syndromes in Fetuses

2021 ◽  
Vol 12 ◽  
Author(s):  
Meiying Cai ◽  
Xianguo Fu ◽  
Liangpu Xu ◽  
Na Lin ◽  
Hailong Huang
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Prenatal Diagnosis ◽  
Copy Number ◽  
De Novo ◽  
Single Nucleotide Polymorphism Array ◽  
Copy Number Variant ◽  
Prenatal Ultrasound ◽  
Nucleotide Polymorphism ◽  
Array Analysis ◽  
Single Nucleotide

Smith-Magenis syndrome and Potocki-Lupski syndrome are rare autosomal dominant diseases. Although clinical phenotypes of adults and children have been reported, fetal ultrasonic phenotypes are rarely reported. A retrospective analysis of 6,200 pregnant women who received invasive prenatal diagnosis at Fujian Provincial Maternal and Child Health Hospital between October 2016 and January 2021 was performed. Amniotic fluid or umbilical cord blood was extracted for karyotyping and single nucleotide polymorphism array analysis. Single nucleotide polymorphism array analysis revealed six fetuses with copy number variant changes in the 17p11.2 region. Among them, one had a copy number variant microdeletion in the 17p11.2 region, which was pathogenically analyzed and diagnosed as Smith-Magenis syndrome. Five fetuses had copy number variant microduplications in the 17p11.2 region, which were pathogenically analyzed and diagnosed as Potocki-Lupski syndrome. The prenatal ultrasound phenotypes of the six fetuses were varied. The parents of two fetuses with Potocki-Lupski syndrome refused verification. Smith-Magenis syndrome in one fetus and Potocki-Lupski in another were confirmed as de novo. Potocki-Lupski syndrome in two fetuses was confirmed to be from maternal inheritance. The prenatal ultrasound phenotypes of Smith-Magenis syndrome and Potocki-Lupski syndrome in fetuses vary; single nucleotide polymorphism array analysis is a powerful diagnostic tool for these diseases. The ultrasonic phenotypes of these cases may enrich the clinical database.

scholarly journals Intracranial calcifications and dystonia associated with a novel deletion of chromosome 8p11.2 encompassing SLC20A2 and THAP1

2019 ◽  
Vol 12 (5) ◽  
pp. e228782 ◽  
Author(s):  
Weiyi Mu ◽  
Laura Tochen ◽  
Caroline Bertsch ◽  
Harvey S Singer ◽  
Kristin W Barañano
Keyword(s):  
Movement Disorders ◽  
Copy Number ◽  
Copy Number Variant ◽  
French Canadian ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Variable Expression ◽  
Canadian Population ◽  
Brain Calcification ◽  
Psychiatric Issues

Several genes located within the chromosome 8p11.21 region are associated with movement disorders including SLC20A2 and THAP1. SLC20A2 is one of four genes associated with primary familial brain calcification, a syndrome that also includes movement disorders, cognitive decline and psychiatric issues. THAP1 is associated with dystonia type 6, a dominantly inherited dystonia with variable expression. In addition, several reports in the French-Canadian population have described microdeletions within the 8p11.2 region presenting with dystonia-plus syndromes including brain calcifications. This case report describes a 12-year-old boy with brain calcifications and generalised dystonia associated with a deletion in the 8p11.2 region detected via single nucleotide polymorphism microarray. This report emphasises the importance of obtaining a microarray analysis in diagnosing movement disorders and suggests that this copy number variant may be an under-recognised cause of dystonia and brain calcifications.

scholarly journals Comparative analyses of seven algorithms for copy number variant identification from single nucleotide polymorphism arrays

2010 ◽  
Vol 38 (9) ◽  
pp. e105-e105 ◽  
Author(s):  
Andrew E. Dellinger ◽  
Seang-Mei Saw ◽  
Liang K. Goh ◽  
Mark Seielstad ◽  
Terri L. Young ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Copy Number ◽  
Copy Number Variant ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Comparative Analyses ◽  
Variant Identification

scholarly journals Construction of thousands of single cell genome sequencing libraries using combinatorial indexing

2016 ◽  
Author(s):  
Sarah A. Vitak ◽  
Kristof A. Torkenczy ◽  
Jimi L. Rosenkrantz ◽  
Andrew J. Fields ◽  
Lena Christiansen ◽  
...  
Keyword(s):  
Single Cell ◽  
Genome Sequencing ◽  
Copy Number ◽  
Low Cost ◽  
Single Cells ◽  
Copy Number Variant ◽  
Tumor Evolution ◽  
Somatic Variation ◽  
Cell Genome ◽  
Single Cell Genome

AbstractSingle cell genome sequencing has proven to be a valuable tool for the detection of somatic variation, particularly in the context of tumor evolution and neuronal heterogeneity. Current technologies suffer from high per-cell library construction costs which restrict the number of cells that can be assessed, thus imposing limitations on the ability to quantitatively measure genomic heterogeneity within a tissue. Here, we present Single cell Combinatorial Indexed Sequencing (SCI-seq) as a means of simultaneously generating thousands of low-pass single cell libraries for the purpose of somatic copy number variant detection. In total, we constructed libraries for 16,698 single cells from a combination of cultured cell lines, frontal cortex tissue from Macaca mulatta, and two human adenocarcinomas. This novel technology provides the opportunity for low-cost, deep characterization of somatic copy number variation in single cells, providing a foundational knowledge across both healthy and diseased tissues.

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