Whole exome sequencing identifies variants in the \(\textit{TNNI3}\) gene in vietnamese patient with restrictive cardiomyopathy - a case report

Nguyen Thi Kim Lien; Van Tung Nguyen; Trong Tu Le; Thi Hai Van Dang; Quynh Nga Vu; Thanh Hien Nguyen; Minh Hien Do; Hoang Lam Nguyen; Tuan Hien Trinh; Minh Duc Nguyen; Huy Hoang Nguyen

doi:10.15625/2615-9023/19255

Author affiliations

Authors

Nguyen Thi Kim Lien Institute of Genome Research
Nguyen Van Tung
Le Trong Tu
Dang Thi Hai Van
Vu Quynh Nga
Nguyen Thanh Hien
Do Minh Hien
Nguyen Hoang Lam
Trinh Tuan Hien
Nguyen Minh Duc
Nguyen Huy Hoang

DOI:

https://doi.org/10.15625/2615-9023/19255

Keywords:

Mutation, Restrictive cardiomyopathy (RCM), TNNI3 gene, Vietnamese patient, Whole exome sequencing (WES).

Abstract

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease in which the heart wall is rigid leading to diastolic dysfunction caused by abnormal elastic properties of the myocardium and/or intercellular matrix. The prognosis is generally poor, and RCM has a high mortality rate in pediatric patients. There are no curative treatments for RCM, so cardiac transplantation is the only effective treatment. Diagnosis RCM, clinical diagnosis can be challenging because clinical presentations and imaging manifestations of RCM are similar to other cardiomyopathies so it requires other specific diagnoses. Currently, pathogenic mutations in 22 different genes have been identified in patients with RCM. Identifying mutations in these genes helps discriminate RCM from other cardiomyopathies. Besides, next-generation sequencing (including whole genome sequencing, whole exome sequencing,...) has provided an effective tool for simultaneously analyzing mutations in many different genes.

In this study, we conducted sequencing of the entire gene coding region (WES) in the patient and identified a compound heterozygote variants (c.289C>G, p.Arg97Gly and c.433C>T, p.Arg145Trp) in the TNNI3 gene. These variants were inherited from the patient's father and mother, who were heterozygous variant carriers. These variants were also identified as the pathogenic variants in the ClinVar database (accession number VCV001331910.2 and VCV000012426.28, respectively) and were the cause of the patient's disease. Our results suggest that WES can be used to definitively diagnose the genetic variants associated with RCM and show that genetic screening is essential for families of RCM patients.

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