Familial Hypertrophic Cardiomyopathy - Identification of cause and risk stratification through exome sequencing

Biswas, Amitabh; Das, Soumi; Kapoor, Mitali; Vellarikkal, Shamsudheen Karuthedath; Jayarajan, Rijith; Verma, Ankit; Seth, Sandeep; Bhargava, Balram; Scaria, Vinod; Sivasubbu, Sridhar; Rao, Vadlamudi Raghavendra

doi:10.1016/j.gene.2018.03.062

Cited by 10 publications

(10 citation statements)

References 17 publications

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“…HCM presents an important familial characteristic. Even considering that ethnic and racial differences can affect the familial history and genetic profile of the affected subjects, around 1,500 mutations in at least 20 genes encoding the myofilaments of the sarcomere or Z-disc have been studied and associated to this condition [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Familial Hypertrophic Cardiomyopathy: Late Potentials and Other Prognostic Markers

Chaves-Markman¹,

Markman

Santos-Veloso

et al. 2020

Cureus

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Familial hypertrophic cardiomyopathy is an autosomal dominant genetic disease considered the most common cause of sudden cardiac death in individuals under 35 years old, especially the athletes. This study aimed to investigate the association between the presence of late potentials and a family history of sudden death, syncope, and complex ventricular arrhythmias on patients with hypertrophic cardiomyopathy. A case series study was carried out from March 2001 to December 2002, including 22 patients with hypertrophic cardiomyopathy according to transthoracic echocardiogram criteria. Patients on a cardiac pacemaker, right bundle branch block, cardiac transplant, and under no possibilities to realize the exams were excluded. The results showed that asymmetric septal hypertrophy was the most common type (73%), 63% had a positive familial history of hypertrophic cardiomyopathy, 55% sudden cardiac death, and 23% syncope. Also, complex ventricular arrhythmias were detected in 14% and late potentials in 23% of patients. According to this study, the presence of late potentials was not associated with familial sudden death, syncope, and complex ventricular arrhythmias.

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Section: Introductionmentioning

confidence: 99%

Familial Hypertrophic Cardiomyopathy: Late Potentials and Other Prognostic Markers

Chaves-Markman¹,

Markman

Santos-Veloso

et al. 2020

Cureus

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“…TNNT2 gene : Biswas et al 33 reported a mutation associated with SCD in TNNT2 gene in a case of familial HCM, where the proband and his brother were found to be carriers of the TNNT2 p.R92W (rs397516456) missense mutation. The proband had left ventricular hypertrophy with atrial fibrillation, was categorized under NYHA class III with severe symptoms and was implanted with ICD.…”

Section: Resultsmentioning

confidence: 99%

Sarcomeric gene variants among Indians with hypertrophic cardiomyopathy: A scoping review

Koshy,

Ganapathi,

Jeemon

et al. 2023

Indian Journal of Medical Research

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Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease that frequently causes sudden cardiac death (SCD) among young adults. Several pathogenic mutations in genes encoding the cardiac sarcomere have been identified as diagnostic factors for HCM and proposed as prognostic markers for SCD. The objective of this review was to determine the scope of available literature on the variants encoding sarcomere proteins associated with SCD reported among Indian patients with HCM. The eligibility criteria for the scoping review included full text articles that reported the results of genetic screening for sarcomeric gene mutations in HCM patients of Indian south Asian ancestry. We systematically reviewed studies from the databases of Medline, Scopus, Web of Science core collection and Google Scholar. The electronic search strategy included a combination of generic terms related to genetics, disease and population. The protocol of the study was registered with Open Science Framework ( https://osf.io/53gde/ ). A total of 19 articles were identified that reported pathogenic or likely pathogenic (P/LP) variants within MYH7, MYBPC3, TNNT2, TNNI3 and TPM1 genes, that included 16 singletons, one de novo and one digenic mutation ( MYH7/ TPM1 ) associated with SCD among Indian patients. Evidence from functional studies and familial segregation implied a plausible mechanistic role of these P/LP variants in HCM pathology. This scoping review has compiled all the P/LP variants reported to-date among Indian patients and summarized their association with SCD. Single homozygous, de novo and digenic mutations were observed to be associated with severe phenotypes compared to single heterozygous mutations. The abstracted genetic information was updated with reference sequence ID (rsIDs) and compiled into freely accessible HCMvar database, available at https://hcmvar.heartfailure.org.in/ . This can be used as a population specific genetic database for reference by clinicians and researchers involved in the identification of diagnostic and prognostic markers for HCM.

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“…Hypertrophic cardiomyopathy (HCM) is a common cause of sudden cardiac death (SCD) in the young [1][2][3]. Significant left ventricular hypertrophy that cannot be explained by other causes is the main clinical feature of HCM [4].…”

Section: Introductionmentioning

confidence: 99%

FLNC and MYLK2 gene mutations in a Chinese family with different phenotypes of cardiomyopathy

Liu

et al. 2020

Preprint

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Background Mutations in the sarcomeric protein filamin C (FLNC) gene have been linked to hypertrophic cardiomyopathy (HCM), in which they increase the risk of ventricular arrhythmia and sudden death. In this study, we identified a novel missense mutation of FLNC in a Chinese family with HCM and interestingly a second novel truncating mutation of MYLK2 in one family member with different phenotype. Methods We performed whole-exome sequencing in a Chinese family with HCM of unknown cause. To validate the function of a novel mutation of FLNC, we introduced the mutant and wild-type gene into AC16 cells (human cardiomyocytes), and used western blotting to analyze the expression of FLNC in subcellular fractions, and confocal microscope to observe the subcellular distribution of the protein. Results We identified a novel missense single nucleotide variant (FLNC c.G5935A [p.A1979T]) in the family, which segregates with the disease. FLNC expression levels were equivalent in both wild type and p.A1979T cardiomyocytes. However, expression of the mutant protein resulted in cytoplasmic protein aggregations, in contrast to wild type FLNC, which was distributed in the cytoplasm and did not form aggregates. Unexpectely, a second truncating mutation, NM_033118:exon8:c.G1138T:p.E380X of the MYLK2 gene, was identified in the mother of the proband with dilated cardiomyopathy, but absent in other subjects. Conclusion We identified the FLNC A1979T mutation as a novel pathogenic variant associated with HCM in a Chinese family, as well as a second causal mutation in a family member with a distinct phenotype. The possibility of more than one causal mutations in cardiomyopathy warrants clinical attention, especially for patients with atypical clinical features.

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Familial Hypertrophic Cardiomyopathy - Identification of cause and risk stratification through exome sequencing

Cited by 10 publications

References 17 publications

Familial Hypertrophic Cardiomyopathy: Late Potentials and Other Prognostic Markers

Familial Hypertrophic Cardiomyopathy: Late Potentials and Other Prognostic Markers

Sarcomeric gene variants among Indians with hypertrophic cardiomyopathy: A scoping review

FLNC and MYLK2 gene mutations in a Chinese family with different phenotypes of cardiomyopathy

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