scholarly journals Identification of Possible Risk Variants of Familial Strabismus Using Exome Sequencing Analysis

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 75
Author(s):  
Joon-Yong An ◽  
Jae Ho Jung ◽  
Leejee Choi ◽  
Eric D. Wieben ◽  
Brian G. Mohney
Keyword(s):  
Exome Sequencing ◽  
Genetic Variants ◽  
Primary Outcome ◽  
Family Members ◽  
Great Promise ◽  
Genetic Profile ◽  
Sequencing Analysis ◽  
Risk Variants ◽  
Whole Exome ◽  
Rare Genetic Variants

Purpose: To investigate candidate genes associated with familial strabismus and propose a theory of their interaction in familial strabismus associated with early neurodevelopment. Methods: Eighteen families, including 53 patients diagnosed with strabismus and 34 unaffected family members, were analyzed. All patients with strabismus and available unaffected family members were evaluated using whole exome sequencing. The primary outcome was to identify rare occurring variants among affected individuals and investigate the evidence of their genetic heterogeneity. These results were compared with exome sequencing analysis to build a comprehensive genetic profile of the study families. Results: We observed 60 variants from 58 genes in 53 patients diagnosed with strabismus. We prioritized the most credible risk variants, which showed clear segregation in family members affected by strabismus. As a result, we found risk variants in four genes (FAT3, KCNH2, CELSR1, and TTYH1) in five families, suggesting their role in development of familial strabismus. In other families, there were several rare genetic variants in affected cases, but we did not find clear segregation pattern across family members. Conclusion: Genomic sequencing holds great promise in elucidating the genetic causes of strabismus; further research with larger cohorts or other related approaches are warranted.

scholarly journals Identification of rare genetic variants in Juvenile Idiopathic Arthritis using whole exome sequencing

2015 ◽  
Vol 13 (S1) ◽  
Author(s):  
E Sanchez ◽  
S Grandemange ◽  
F Tran Mau-Them ◽  
P Louis-Plence ◽  
A Carbasse ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Whole Exome ◽  
Rare Genetic Variants

Identification of Novel Genes Associated to Major Mental Disease by Whole Exome Sequencing in Families with High Prevalence

2017 ◽  
Vol 41 (S1) ◽  
pp. S98-S99
Author(s):  
J. Pol Fuster ◽  
L. Ruiz Guerra ◽  
B. Ortega Vila ◽  
A. Medina Dols ◽  
B. Bisbal Carrió ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Mental Disease ◽  
Psychotic Symptoms ◽  
Disease Etiology ◽  
New Genes ◽  
Whole Exome ◽  
High Prevalence ◽  
Rare Genetic Variants

IntroductionThe identification of new genetic variants underlying psychosis is crucial to improve its molecular diagnosis and to determine the disease etiology, which is necessary to develop new therapeutic targets.AimTo identify novel rare genetic variants associated to mental disorders, using whole exome sequencing (WES).MethodsTwo families with high prevalence of mental disease were genotyped using WES. The first family has 5 members affected, the mother with a bipolar disorder, three sons, two with schizophrenia and one with schizoaffective disorder, and a cousin with major depression and psychotic symptoms. The second family is constituted by 38 members affected by major mental diseases in three generations. Key affected members of each family were genotyped by WES. Shared rare variants, with allelic frequencies below 0.5% in general population, were identified among the affected members of the family. The segregation of those variants was confirmed by Sanger sequencing.ResultsIn family 1, thirty-seven genetic variants related to neurodevelopment were identified. Two of those variants in the genes TRIP12 and RNF25 segregated with psychosis. In family 2, seven rare genetic variants contained in genes related to neurodevelopment were identified. A mutation in the gene ARHGAP19 segregated with psychosis.ConclusionsThree new genes have been found to be associated with psychosis. TRIP12 and RNF25 encode two E3-ubiquitin ligases which modulate the Wnt pathway, mutations in which lead to neurodevelopmental defects. ARHGAP19 encodes a GTPase which regulates the RhoA protein, involved in the regulation of the cytoskeleton.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Whole-Exome sequencing identifies a Type 2 Diabetes candidate mutation in PTPRF

2020 ◽  
Author(s):  
Erik J.M. Toonen ◽  
Michael Kwint ◽  
Alexander Hoischen ◽  
Cees J. Tack
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Association Studies ◽  
Family Members ◽  
Genome Wide Association Studies ◽  
Whole Exome

Objectives: Identification of genetic factors involved in Type 2 diabetes mellitus (T2DM) has been challenging. While genome-wide association studies (GWAS) have identified over 60 loci associated with T2DM, these variants only explain a small proportion of the total heritability of the disease. Whole-exome sequencing has become a powerful approach to identify genetic variants that are not captured by GWAS. We applied exome sequencing to identify causal genetic variants in a family with a 2-generation history of T2DM characterized by substantial insulin resistance, hypertension and isolated hypertriglyceridemia. Methods: Exome sequencing was performed on genomic DNA of two affected family members. Twenty-four identified variants that were present in both family members were further tested for segregation in all other family members by Sanger sequencing. Results: Three rare missense variants, located in the genes PTPRF, FUCA1 and FBXO30, were present in all affected family members but also in one unaffected family member. Protein-protein interaction analysis showed that PTPRF strongly interacts with several members of the insulin signaling pathway. Conclusions: Our results suggest that the variant in the PTPRF gene might be causal for an unusual T2DM subtype that is characterized by a severe insulin resistance and isolated hypertriglyceridemia.

scholarly journals Whole-exome sequencing with targeted analysis and epilepsy after acute symptomatic neonatal seizures

2021 ◽  
Author(s):  
Adam L. Numis ◽  
Gilberto da Gente ◽  
Elliott H. Sherr ◽  
Hannah C. Glass
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
List Type ◽  
Sequencing Analysis ◽  
Neonatal Seizures ◽  
Pathogenic Variants ◽  
Targeted Analysis ◽  
Whole Exome ◽  
Epilepsy Gene

Abstract Background The contribution of pathogenic gene variants with development of epilepsy after acute symptomatic neonatal seizures is not known. Methods Case–control study of 20 trios in children with a history of acute symptomatic neonatal seizures: 10 with and 10 without post-neonatal epilepsy. We performed whole-exome sequencing (WES) and identified pathogenic de novo, transmitted, and non-transmitted variants from established and candidate epilepsy association genes and correlated prevalence of these variants with epilepsy outcomes. We performed a sensitivity analysis with genes associated with coronary artery disease (CAD). We analyzed variants throughout the exome to evaluate for differential enrichment of functional properties using exploratory KEGG searches. Results Querying 200 established and candidate epilepsy genes, pathogenic variants were identified in 5 children with post-neonatal epilepsy yet in only 1 child without subsequent epilepsy. There was no difference in the number of trios with non-transmitted pathogenic variants in epilepsy or CAD genes. An exploratory KEGG analysis demonstrated a relative enrichment in cell death pathways in children without subsequent epilepsy. Conclusions In this pilot study, children with epilepsy after acute symptomatic neonatal seizures had a higher prevalence of coding variants with a targeted epilepsy gene sequencing analysis compared to those patients without subsequent epilepsy. Impact We performed whole-exome sequencing (WES) in 20 trios, including 10 children with epilepsy and 10 without epilepsy, both after acute symptomatic neonatal seizures. Children with post-neonatal epilepsy had a higher burden of pathogenic variants in epilepsy-associated genes compared to those without post-neonatal epilepsy. Future studies evaluating this association may lead to a better understanding of the risk of epilepsy after acute symptomatic neonatal seizures and elucidate molecular pathways that are dysregulated after brain injury and implicated in epileptogenesis.

scholarly journals NAPG mutation in family members with hereditary hemorrhagic telangiectasia in China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Xu ◽  
Yong-Biao Zhang ◽  
Li-Jun Liang ◽  
Jia-Li Tian ◽  
Jin-Ming Lin ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Sanger Sequencing ◽  
Conformational Stability ◽  
Sequencing Analysis ◽  
Large Pedigree ◽  
Whole Exome ◽  
Variant Filtering ◽  
Genetic Contributions

Abstract Background Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations in the skin and mucous membranes. We enrolled a large pedigree comprising 32 living members, and screened for mutations responsible for HHT. Methods We performed whole-exome sequencing to identify novel mutations in the pedigree after excluding three previously reported HHT-related genes using Sanger sequencing. We then performed in silico functional analysis of candidate mutations that were obtained using a variant filtering strategy to identify mutations responsible for HHT. Results After screening the HHT-related genes, activin A receptor-like type 1 (ACVRL1), endoglin (ENG), and SMAD family member 4 (SMAD4), we did not detect any co-segregated mutations in this pedigree. Whole-exome sequencing analysis of 7 members and Sanger sequencing analysis of 16 additional members identified a mutation (c.784A > G) in the NSF attachment protein gamma (NAPG) gene that co-segregated with the disease. Functional prediction showed that the mutation was deleterious and might change the conformational stability of the NAPG protein. Conclusions NAPG c.784A > G may potentially lead to HHT. These results expand the current understanding of the genetic contributions to HHT pathogenesis.

scholarly journals Analysis workflow to assess de novo genetic variants from human whole-exome sequencing

2021 ◽  
Vol 2 (1) ◽  
pp. 100383
Author(s):  
Nicholas S. Diab ◽  
Spencer King ◽  
Weilai Dong ◽  
Garrett Allington ◽  
Amar Sheth ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
De Novo ◽  
Whole Exome ◽  
Analysis Workflow

scholarly journals TP53 and PTEN mutations were shared in concurrent germ cell tumor and acute megakaryoblastic leukemia

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Keiichi Akizuki ◽  
Masaaki Sekine ◽  
Yasunori Kogure ◽  
Takuro Kameda ◽  
Kotaro Shide ◽  
...  
Keyword(s):  
Germ Cell ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Germ Cell Tumor ◽  
Somatic Mutations ◽  
Cell Tumor ◽  
Sequencing Analysis ◽  
Male Adult ◽  
Clonal Relationship ◽  
Whole Exome

Abstract Background The occurrence of a mediastinal germ cell tumor (GCT) and hematological malignancy in the same patient is very rare. Due to its rarity, there have been only two reports of the concurrent cases undergoing detailed genetic analysis with whole-exome sequencing (WES), and the possible clonal relationship between the both tumors remained not fully elucidated. Methods We performed whole-exome sequencing analysis of mediastinal GCT and acute myeloid leukemia (AML) samples obtained from one young Japanese male adult patient with concurrent both tumors, and investigated the possible clonal relationship between them. Results Sixteen somatic mutations were detected in the mediastinal GCT sample and 18 somatic mutations in the AML sample. Mutations in nine genes, including TP53 and PTEN both known as tumor suppressor genes, were shared in both tumors. Conclusions All in our case and in the previous two cases with concurrent mediastinal GCT and AML undergoing with whole-exome sequencing analysis, TP53 and PTEN mutations were commonly shared in both tumors. These data not only suggest that these tumors share a common founding clone, but also indicate that associated mediastinal GCT and AML harboring TP53 and PTEN mutations represent a unique biological entity.

scholarly journals Ablepharon macrostomia syndrome in a Thai patient: case report and literature review

2020 ◽  
Vol 14 (2) ◽  
pp. 83-88
Author(s):  
Phawin Kor-anantakul ◽  
Kanya Suphapeetiporn ◽  
Somchit Jaruratanasirikul
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sequencing Analysis ◽  
Patient Case ◽  
Thai Patient ◽  
Labia Minora ◽  
Whole Exome ◽  
Rare Congenital Disorder

AbstractAblepharon macrostomia syndrome (AMS) is a rare congenital disorder. To our knowledge, only 20 cases have been reported to date, and all in patients from Western countries. We report a case of AMS in a Thai patient, who presented at age 3 months with severe ectropion of both upper and lower eyelids, alopecia totalis, no palpable clitoris, and hypoplasia of both labia minora and labia majora. Trio whole exome sequencing analysis was performed, which revealed a heterozygous missense c.223G>A (p.Glu75Lys) variation in TWIST2. To our knowledge, this is the first reported case of AMS in a patient from Thailand and the first reported case of AMS in Asia.

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