Identification of genetic variants in two Vietnamese patients with hypertrophic cardiomyopathy by whole exome sequencing

Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease and a major cause of sudden death. It is also involved in increasing morbidity and mortality of various cardiovascular diseases. Genetic factors have been found to be important in determining the phenotypic manifestation of cardiac hypertrophy. However, only 50–60% of HCM patients have been identified as having pathogenic variants in known genes, suggesting that more studies are needed to find more disease genes. In this study, whole exome sequencing was performed on two patients from two unrelated families who were diagnosed with HCM to screen the associated mutations.
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Identification of genetic variants in two Vietnamese patients with hypertrophic cardiomyopathy by whole exome sequencingVietnam Journal of Biotechnology 22(2): 212-226, 2024. DOI: 10.15625/vjbt-19499IDENTIFICATION OF GENETIC VARIANTS IN TWO VIETNAMESEPATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY BY WHOLEEXOME SEQUENCINGNguyen Thi Kim Lien1,, Nguyen Van Tung 1, Le Trong Tu 2,3, Dang Thi Hai Van 2,Vu Quynh Nga3, Nguyen Ngoc Lan1, Nguyen Thanh Hien1, Le Tat Thanh1,Nguyen Minh Duc 1,4, Nguyen Huy Hoang11Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam2 Hanoi Medical University, Ministry of Health, Hanoi, Vietnam3 Hanoi Heart Hospital, Ministry of Health, Hanoi, Vietnam4 National Research Center for Medicinal Plant Germplasm and Breeding, National Instituteof Medicinal Materials, Hanoi, Vietnam To whom correspondence should be addressed. E-mail: ntkimlienibt@gmail.com Received: 27.11.2023 Accepted: 18.06.2024 ABSTRACT Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease and a major cause of sudden death. It is also involved in increasing morbidity and mortality of various cardiovascular diseases. Genetic factors have been found to be important in determining the phenotypic manifestation of cardiac hypertrophy. However, only 50–60% of HCM patients have been identified as having pathogenic variants in known genes, suggesting that more studies are needed to find more disease genes. In this study, whole exome sequencing was performed on two patients from two unrelated families who were diagnosed with HCM to screen the associated mutations. Two heterozygous variants c.836A>C (p.Tyr279Ser) in the PTPN11 gene and c.83A>C, (p.His28Pro) in the PRKAG2 gene have been identified in patients 1 and 2, respectively. Assessment of the level of impact using prediction software shows that these are potentially harmful variants and may be the cause of disease in patients. Our results provided an understanding of the cause of the patient’s disease, helping clinicians diagnose and provide better genetic counseling to the patients’ family. Keywords: hypertrophic cardiomyopathy (HCM), PRKAG2, PTPN11, variant, Vietnamese patient, whole exome sequencing (WES).INTRODUCTION cardiac death (SCD) in adolescents (Marian, Braunwald, 2017). HCM is characterized byHypertrophic cardiomyopathy (HCM) is hypertrophy of the ventricular myocardium,considered the leading cause of sudden which results from increased sensitivity to212Vietnam Journal of Biotechnology 22(2): 212-228, 2024. DOI: 10.15625/vjbt-19499calcium. Cardiac hypertrophy is defined as Maron, 2018). The weak genotype-an increase in the mass of the heart muscle. phenotype correlation and wide phenotypicHCM is the most common genetic variability of the disease are the causes thatcardiovascular disease, and the prevalence limit the ability to use genetics for definitiveof HCM is approximately 1: 500 in young diagnosis (Mogensen et al., 2004; Tower-individuals (Marian, 2008). The prevalence Rader et al., 2017).may be higher in older people because the Genetic advances (next-generationpenetrance of causative variants is age- sequencing) have improved knowledgedependent. The prevalence ranges from 0.02 about HCM at the molecular level andto 0.2% in Western countries (Maron et al., provided clinical genetic testing. Early2016) and Asian countries (Moon et al., diagnosis of HCM is important for providing2020; Bai et al., 2022). Heritability of the appropriate treatment and preventiondiseases in the general population was strategies for patients as well as clinicalestimated to be from 20 to 70% (Sharma et surveillance and genetic counseling foral., 2006). The clinical manifestations of family members (Elliott et al., 2014). WangHCM include heart failure (HF) (Maron et et al. (2017) provided a list of 44 genesal., 2018), stroke (Fauchier et al., 2022), related to HCM. HCM is primarily inheritedatrial fibrillation (AF) (Garg et al., 2019), as an autosomal dominant trait by variationsarrhythmia, and SCD. SCD is the first and in the gene encoding the sarcomere proteinmost serious manifestation of the disease (Elliott et al., 2014).and usually occurs in otherwise healthy andasymptomatic young people (Elliott et al., Variants in the PTPN11 gene that encodes2006). Of all SCD cases in people aged 5 to for the protein tyrosine phosphatase (PTP),34 years, 14% were determined to be due to SHP2, nonreceptor type ...