Whole exome sequencing identifies a novel mutation (c.333 + 2T > C) of TNNI3K in a Chinese family with dilated cardiomyopathy and cardiac conduction disease

Gene ◽  
2018 ◽  
Vol 648 ◽  
pp. 63-67 ◽  
Author(s):  
Liang-Liang Fan ◽  
Hao Huang ◽  
Jie-Yuan Jin ◽  
Jing-Jing Li ◽  
Ya-Qin Chen ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Cardiac Conduction ◽  
Chinese Family ◽  
Whole Exome

scholarly journals Whole-Exome Sequencing Identifies a Novel TRPM4 Mutation in a Chinese Family with Atrioventricular Block

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Yi Dong ◽  
Ran Du ◽  
Liang-liang Fan ◽  
Jie-yuan Jin ◽  
Hao Huang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Atrioventricular Block ◽  
Transient Receptor Potential ◽  
Novel Mutation ◽  
Receptor Potential ◽  
Cardiac Conduction ◽  
Chinese Family ◽  
Transient Receptor Potential Melastatin ◽  
Whole Exome

Atrioventricular block (AVB) is a leading cause of sudden cardiac death, and most of AVB cases are presented as autosomal dominant. The electrocardiogram of AVB patients presents an abnormal progressive cardiac conduction disorder between atria and ventricles. Transient receptor potential melastatin 4 (TRPM4) is a nonselective Ca2+-activated cation channel gene defined as a novel disease-causing gene of AVB. So far, 47 mutations of TRPM4 have been recorded in Human Gene Mutation Database. The aim of this study was to explore the relationship between TRPM4 mutation and pathogenesis of AVB. We investigated a Chinese family with AVB by whole-exome sequencing. An arrhythmia-related gene filtering strategy was used to analyze the disease-causing mutations. Three different bioinformatics programs were used to predict the effects of the mutation result. A novel mutation of TRPM4 was identified (c.2455C>T/p.R819C) and cosegregated in the affected family members. The three bioinformatics programs predicted that the novel mutation may lead to damage. Our study will contribute to expand the spectrum of TRPM4 mutations and supply accurate genetic testing information for further research and the clinical therapy of AVB.

Whole-Exome Sequencing Identifies a Novel Mutation (p.L320R) of Alpha-Actinin 2 in a Chinese Family with Dilated Cardiomyopathy and Ventricular Tachycardia

2019 ◽  
Vol 157 (3) ◽  
pp. 148-152 ◽  
Author(s):  
Liang-Liang Fan ◽  
Hao Huang ◽  
Jie-Yuan Jin ◽  
Jing-Jing Li ◽  
Ya-Qin Chen ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Dilated Cardiomyopathy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Pathogenic Mutation ◽  
Left Ventricular ◽  
Chinese Family ◽  
Whole Exome

Dilated cardiomyopathy (DCM) is a severe cardiovascular disease which can lead to heart failure and sudden cardiac death (SCD). The typical feature of DCM is left ventricular enlargement or dilatation. In some conditions, DCM and arrhythmia can occur concurrently, apparently promoting the prevalence of SCD. According to previous studies, mutations in more than 100 genes have been detected in DCM and/or arrhythmia patients. Here, we report a Chinese family with typical DCM, ventricular tachycardia, syncope, and SCD. Using whole-exome sequencing, a novel, likely pathogenic mutation (c.959T>G/p.L320R) of actinin alpha 2 (ACTN2) was identified in all affected family members. This novel mutation was also predicted to be disease-causing by MutationTaster, SIFT, and Polyphen-2. Our study not only expands the spectrum of ACTN2 mutations and contributes to the genetic diagnosis and counseling of the family, but also provides a new case with overlap phenotype that may be caused by the ACTN2 variant.

A novel heterozygous variant p.(Trp538Arg) of SYNM is identified by whole‐exome sequencing in a Chinese family with dilated cardiomyopathy

2018 ◽  
Vol 83 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Shu‐Bing Zhang ◽  
Yu‐Xing Liu ◽  
Liang‐Liang Fan ◽  
Hao Huang ◽  
Jing‐Jing Li ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Chinese Family ◽  
Whole Exome ◽  
Heterozygous Variant

scholarly journals Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing

2014 ◽  
Vol 15 (8) ◽  
pp. 727-734 ◽  
Author(s):  
Nan Hong ◽  
Yan-hua Chen ◽  
Chen Xie ◽  
Bai-sheng Xu ◽  
Hui Huang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Chinese Family ◽  
Whole Exome

scholarly journals A novel SPAST gene mutation identified in a Chinese family with hereditary spastic paraplegia

2020 ◽  
Author(s):  
Weiwei Yu ◽  
Haiqiang Jin ◽  
Jianwen Deng ◽  
Ding Nan ◽  
Yining Huang
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Hereditary Spastic Paraplegia ◽  
Dna Isolation ◽  
Tertiary Structure ◽  
Novel Mutation ◽  
Chinese Family ◽  
Spastic Paraplegia ◽  
Whole Exome ◽  
And Function

Abstract Background: Hereditary spastic paraplegia is a heterogeneous group of clinically and genetically neurodegenerative diseases characterized by progressive gait disorder. Hereditary spastic paraplegia can be inherited in various ways, and all modes of inheritance are associated with multiple genes or loci. At present, more than 76 disease-causing loci have been identified in hereditary spastic paraplegia patients. Here, we report a novel mutation in SPAST gene associated with hereditary spastic paraplegia in a Chinese family, further enriching the hereditary spastic paraplegia spectrum. Methods: Whole genomic DNA was extracted from peripheral blood of the 15 subjects from a Chinese family using DNA Isolation Kit. The Whole Exome Sequencing of the proband was analyzed and the result was identified in the rest individuals. RaptorX prediction tool and Protein Variation Effect Analyzer were used to predict the effects of the mutation on protein tertiary structure and function.Results: Spastic paraplegia has been inherited across at least four generations in this family, during which only four HSP patients were alive. The results obtained by analyzing the Whole Exome Sequencing of the proband exhibited a novel disease-associated in-frame deletion in the SPAST gene, and the this mutation also existed in the rest three HSP patients in this family. This in-frame deletion consists of three nucleotides deletion (c.1710_1712delGAA) within the exon 16, resulting in lysine deficiency at the position 570 of the protein (p.K570del). This novel mutation was also predicted to result in the synthesis of misfolded SPAST protein and have the deleterious effect on the function of SPAST protein.Conclusion: In this case, we reported a novel mutation in the known SPAST gene that segregated with HSP disease, which can be inherited in each generation. Simultaneously, this novel discovery significantly enriches the mutation spectrum, which provides an opportunity for further investigation of genetic pathogenesis of HSP.

scholarly journals A Novel DES L115F Mutation Identified by Whole Exome Sequencing is Associated with Inherited Cardiac Conduction Disease

2019 ◽  
Vol 20 (24) ◽  
pp. 6227 ◽  
Author(s):  
Lung-An Hsu ◽  
Yu-Shien Ko ◽  
Yung-Hsin Yeh ◽  
Chi-Jen Chang ◽  
Yi-Hsin Chan ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Structural Model ◽  
Coiled Coil ◽  
Cytoskeletal Proteins ◽  
Cardiac Conduction ◽  
Chinese Family ◽  
Cardiac Ion Channels ◽  
Whole Exome ◽  
Genes Encoding

Inherited cardiac conduction disease (CCD) is rare; it is caused by a large number of mutations in genes encoding cardiac ion channels and cytoskeletal proteins. Recently, whole-exome sequencing has been successfully used to identify causal mutations for rare monogenic Mendelian diseases. We used trio-based whole-exome sequencing to study a Chinese family with multiple family members affected by CCD, and identified a heterozygous missense mutation (c.343C>T, p.Leu115Phe) in the desmin (DES) gene as the most likely candidate causal mutation for the development of CCD in this family. The mutation is novel and is predicted to affect the conformation of the coiled-coil rod domain of DES according to structural model prediction. Its pathogenicity in desmin protein aggregation was further confirmed by expressing the mutation, both in a cellular model and a CRISPR/CAS9 knock-in mouse model. In conclusion, our results suggest that whole-exome sequencing is a feasible approach to identify candidate genes underlying inherited conduction diseases.

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