Unveiling the genetic variation of severe continuous/mixed-type ossification of the posterior longitudinal ligament by whole-exome sequencing and bioinformatic analysis

2021 ◽  
Author(s):  
Chang-Hyun Lee ◽  
Ki Tae Kim ◽  
Chi Heon Kim ◽  
Eun Young Lee ◽  
Sang Gu Lee ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Mixed Type ◽  
Posterior Longitudinal Ligament ◽  
Bioinformatic Analysis ◽  
Whole Exome

scholarly journals Pathogenic variants identified using whole-exome sequencing in Chinese patients with primary ciliary dyskinesia

2021 ◽  
Author(s):  
Yutian Ye ◽  
Qijun Huang ◽  
Lipeng Chen ◽  
Chunxian Liang ◽  
Kaixue Zhuang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Primary Ciliary Dyskinesia ◽  
Rare Variants ◽  
Genetic Disorders ◽  
Autosomal Recessive Disorder ◽  
Bioinformatic Analysis ◽  
Chinese Patients ◽  
Whole Exome ◽  
Ciliary Dyskinesia

Abstract Background Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder. The genetic factors contributing to PCD pathogenesis remain elusive for approximately 20–35% of patients with complex and abnormal clinical phenotypes. Our study aimed to identify causative variants of sporadic PCD genes using whole-exome sequencing (WES). Result All patients were diagnosed with PCD based on clinical phenotype or transmission electron microscopy (TEM) images of cilia. WES and bioinformatic analysis were then conducted for patients with PCD. Identified candidate variants were validated by Sanger sequencing. Pathogenicity of candidate variants was then evaluated using in silico software and the American College of Medical Genetics and Genomics (ACMG) database. In total, 15 rare variants were identified in five patients with PCD. Five new variants of CCDC40, DNAH1, DNAAF3, and DNAI1 were considered causative variants and included one splicing and three homozygous variants. Conclusion Our study demonstrated that patients with PCD carry rare causative variants of multiple genes. Our findings indicated that not only known causative genes but also other functional genes should be considered for heterogeneous genetic disorders.

scholarly journals A Rare Variant of ANK3 Is Associated With Intracranial Aneurysm

2021 ◽  
Vol 12 ◽  
Author(s):  
Junyu Liu ◽  
Xin Liao ◽  
Jilin Zhou ◽  
Bingyang Li ◽  
Lu Xu ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Intracranial Aneurysm ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Vascular Endothelial Cells ◽  
Association Studies ◽  
Bioinformatic Analysis ◽  
Cell Junctions ◽  
Whole Exome ◽  
Sporadic Cases

Intracranial aneurysm (IA) is a cerebrovascular disorder in which abnormal dilation of a blood vessel results from weakening of the blood vessel wall. The aneurysm may rupture, leading to subarachnoid hemorrhage with severe outcomes. This study was conducted to identify the genetic factors involved in the etiology of IA. Whole-exome sequencing was performed in three IA-aggregate families to identify candidate variants. Further association studies of candidate variants were performed among sporadic cases and controls. Bioinformatic analysis was used to predict the functions of candidate genes and variants. Twenty variants were identified after whole-exome sequencing, among which eight were selected for replicative association studies. ANK3 c.4403G>A (p.R1468H) was significantly associated with IA (odds ratio 4.77; 95% confidence interval 1.94–11.67; p-value = 0.00019). Amino acid R1468 in ANK3 was predicted to be located in the spectrin-binding domain of ankyrin-G and may regulate the migration of vascular endothelial cells and affect cell–cell junctions. Therefore, the variation p.R1468H may cause weakening of the artery walls, thereby accelerating the formation of IA. Thus, ANK3 is a candidate gene highly related to IA.

scholarly journals Next-generation sequencing refines the genetic architecture of Greek GnRH-deficient patients

2019 ◽  
Vol 8 (5) ◽  
pp. 468-480 ◽  
Author(s):  
M I Stamou ◽  
P Varnavas ◽  
L Plummer ◽  
V Koika ◽  
N A Georgopoulos
Keyword(s):  
Genetic Variation ◽  
Next Generation Sequencing ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Wide Spectrum ◽  
Next Generation ◽  
Whole Exome ◽  
Low Prevalence ◽  
Generation Sequencing

Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is a rare disease with a wide spectrum of reproductive and non-reproductive clinical characteristics. Apart from the phenotypic heterogeneity, IGD is also highly genetically heterogeneous with >35 genes implicated in the disease. Despite this genetic heterogeneity, genetic enrichment in specific subpopulations has been described. We have previously described low prevalence of genetic variation in the Greek IGD cohort discovered with utilization of Sanger sequencing in 14 known IGD genes. Here, we describe the expansion of genetic screening in the largest IGD Greek cohort that has ever been studied with the usage of whole-exome sequencing, searching for rare sequencing variants (RSVs) in 37 known IGD genes. Even though Sanger sequencing detected genetic variation in 21/81 IGD patients in 7/14 IGD genes without any evidence of oligogenicity, whole exome sequencing (WES) revealed that 27/87 IGD patients carried a rare genetic change in a total of 15 genes with 4 IGD cases being oligogenic. Our findings suggest that next-generation sequencing (NGS) techniques can discover previously undetected variation, making them the standardized method for screening patients with rare and/or more common disorders.

scholarly journals Unveiling a sudden unexplained death case by whole exome sequencing and bioinformatic analysis

2020 ◽  
Vol 8 (4) ◽  
Author(s):  
Martina Modena ◽  
Vincenzo Castiglione ◽  
Paolo Aretini ◽  
Chiara M. Mazzanti ◽  
Enrica Chiti ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Bioinformatic Analysis ◽  
Sudden Unexplained Death ◽  
Unexplained Death ◽  
Death Case ◽  
Whole Exome

Whole exome sequencing in unclassified autoinflammatory diseases: more monogenic diseases in the pipeline?

Rheumatology ◽  
2020 ◽  
Author(s):  
Can Kosukcu ◽  
Ekim Z Taskiran ◽  
Ezgi Deniz Batu ◽  
Erdal Sag ◽  
Yelda Bilginer ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Disease Onset ◽  
Cost Effective ◽  
Bioinformatic Analysis ◽  
Autoinflammatory Diseases ◽  
Whole Exome ◽  
Monogenic Diseases ◽  
Strong Candidate ◽  
Generation Sequencing

Abstract Objective Autoinflammatory diseases (AIDs) are characterized by recurrent sterile systemic inflammation attacks. More than half of the patients remain genetically undiagnosed with next-generation sequencing panels for common AIDs. In this study, we aimed to define phenotype-genotype correlations in a cohort of unclassified AID patients via whole exome sequencing (WES). Methods Patients with features of AIDs were included in this study followed in the Department of Pediatric Rheumatology at Hacettepe University. They were first screened for MEFV with Sanger sequencing and then WES performed for the patients with clinically insignificant results. Pre-analysis of WES data was done by considering the 13 most common AID-related genes. Further bioinformatic analysis was performed if the patient remained genetically undiagnosed. Results The median age at disease onset was 1.2 years (range 0.2–16) and at the time of study recruitment was 14 years (range 3.5–17). In our cohort, WES provided a definite or probable disease-causing variant in 4 of 11 patients (36%). Heterozygous mutations for two of these genes were previously associated with neurological defects (ADAM17, TBK1), also homozygous ADAM17 mutations were observed in one family with neonatal inflammatory skin and bowel disease. Besides, two genes (LIG4, RAG1) were associated with immunodeficiency although the patients had presented with inflammatory features. Finally, for one patient, we associated a strong candidate gene (NLRC3) with autoinflammatory features. Conclusion WES strategy is cost-effective and provides substantial results for a selected group of undefined AID patients. Our results will contribute to the spectrum of unclassified AIDs.

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