Identification of a novel missense mutation in the TPM1 gene via exome sequencing in a Chinese family with dilated cardiomyopathy

Objectives: Dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death. So far, only 127 mutations of Titin(TTN) have been reported in patients with different phenotypes such as isolated cardiomyopathies, purely skeletal muscle phenotypes or complex overlapping disorders of muscles. Methods: We applied whole-exome sequencing (WES) to investigate cardiomyopathy patients and a cardiomyopathy-related gene-filtering strategy was used to analyze the disease-causing mutations. Sanger sequencing was applied to confirm the mutation cosegregation in the affected families. Results: A nonsense mutation (c.12325C>T/p.R4109X) and a missense mutation (c.17755G>C/p.G5919R) of TTN were identified in 2 Chinese DCM families, respectively. Both mutations were cosegregated in all affected members of both families. The nonsense mutation is predicted to result in a truncated TTN protein and the missense mutation leads to a substitution of glycine by arginine. Both variants may cause the structure changes of titin protein. Conclusions: We employed WES to detect the mutations of DCM patients and identified 2 novel mutations. Our study expands the spectrum of TTN mutations and offers accurate genetic testing information for DCM patients who are still clinically negative.

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Exome sequencing reveals a novel MFN2 missense mutation in a Chinese family with Charcot‑Marie‑Tooth type 2A

Experimental and Therapeutic Medicine ◽

10.3892/etm.2018.6513 ◽

2018 ◽

Cited By ~ 1

Author(s):

Yi You ◽

Xiaodong Wang ◽

Shan Li ◽

Xiuli Zhao ◽

Xue Zhang

Keyword(s):

Exome Sequencing ◽

Missense Mutation ◽

Chinese Family ◽

Charcot Marie Tooth ◽

Tooth Type

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Whole-exome sequencing identifies a Novel SCN5A mutation (C335R) in a Chinese family with arrhythmia

Cardiology in the Young ◽

10.1017/s1047951117002980 ◽

2018 ◽

Vol 28 (5) ◽

pp. 688-691 ◽

Cited By ~ 2

Author(s):

Hao Huang ◽

Dong-Bo Ding ◽

Liang-Liang Fan ◽

Jie-Yuan Jin ◽

Jing-Jing Li ◽

...

Keyword(s):

Exome Sequencing ◽

Missense Mutation ◽

Whole Exome Sequencing ◽

Chinese Family ◽

Illumina Hiseq ◽

Α Subunit ◽

Pathogenic Genes ◽

Whole Exome ◽

Gene Filtering ◽

Protein Dysfunction

AbstractBackgroundSCN5A encodes sodium-channel α-subunit Nav1.5. The mutations of SCN5A can lead to hereditary cardiac arrhythmias such as the long-QT syndrome type 3 and Brugada syndrome. Here we sought to identify novel mutations in a family with arrhythmia.MethodsGenomic DNA was isolated from blood of the proband, who was diagnosed with atrial flutter. Illumina Hiseq 2000 whole-exome sequencing was performed and an arrhythmia-related gene-filtering strategy was used to analyse the pathogenic genes. Sanger sequencing was applied to verify the mutation co-segregated in the family.Results and conclusionsA novel missense mutation in SCN5A (C335R) was identified, and this mutation co-segregated within the affected family members. This missense mutation was predicted to result in amplitude reduction in peak Na+ current, further leading to channel protein dysfunction. Our study expands the spectrum of SCN5A mutations and contributes to genetic counselling of families with arrhythmia.

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Exome Sequencing Identifies a Novel DES Mutation (R227C) in a Chinese Dilated Cardiomyopathy Family

Cardiology ◽

10.1159/000455181 ◽

2017 ◽

Vol 137 (2) ◽

pp. 78-82 ◽

Cited By ~ 6

Author(s):

Rong Yu ◽

Lv Liu ◽

Chan Chen ◽

Jin-Mei Shen

Keyword(s):

Dilated Cardiomyopathy ◽

Exome Sequencing ◽

Genetic Factors ◽

Novel Mutation ◽

Genetic Diagnosis ◽

Chinese Family ◽

Common Disease ◽

Disease Genes ◽

Whole Exome ◽

Gene Filtering

Objectives: Dilated cardiomyopathy (DCM) is a common disease in the clinic, and it is the leading cause of heart failure and sudden cardiac death. Previous studies have proven that genetic factors play a crucial role in the occurrence of DCM; more than 50 disease genes including desmin (DES) have been identified to be associated with DCM. At present, most DES mutations are reported in desmin-related myofibrilla myopathy patients, but variants leading to isolated DCM are rarely reported. Methods: We applied whole-exome sequencing and cardiomyopathy-related gene filtering strategies to discover the genetic factors in a Chinese DCM family. Results: A novel mutation (c.679 C>T /p.R227C) in exon 3 of DES was identified and cosegregated with the affected members of a Chinese family with isolated DCM phenotypes (left ventricle and left atrial diameters). Conclusion: This mutation leads to a substitution of arginine by cysteine and it is predicted to be deleterious by bioinformatics programs. Our study not only contributes to the genetic diagnosis and counseling of families with DCM, but it also further proves that DES mutations may lead to isolated DCM and provides a new case for the study of the relationship between DES mutations and DCM.

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