Novel Association of a De Novo
            <i>CALM2</i>
            Mutation With Long QT Syndrome and Hypertrophic Cardiomyopathy

Zahavich, Laura; Tarnopolsky, Mark A.; Yao, Roderick; Mital, Seema

doi:10.1161/circgen.118.002255

Cited by 15 publications

(11 citation statements)

References 5 publications

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“…Sinus bradycardia might be a manifestation of LQTS in the fetus [11]. Additionally, with reference to previously reported findings [8][9][10], we highly suspect thatCALM2 variants might be associated with cardiomyopathy and arrhythmia, especially LQTS. Nonetheless, further research is required to confirm this hypothesis and elucidate the pathogenic mechanism.…”

Section: Discussionmentioning

confidence: 54%

“…CALM2 is a Ca 2+ -signaling gene that encodes for calmodulin and is associated with long QT syndrome (LQTS) phenotypes. In three reported cases, CALM2 mutation might have contributed to LQTS accompanied by cardiomyopathy (one case of hypertrophic cardiomyopathy and two cases of left ventricular noncompaction cardiomyopathy), indicating the variant positions in CALM2 (c.396T>G;p.D132E, c.394G>C;p.D132H, and c395A>G;p.D132G) [8][9][10]. Our case is the first report of a novel CALM2 mutation (c.389A>G;p.D130G) in fetal noncompaction cardiomyopathy accompanied by bradycardia detected with whole-exome sequencing.…”

Section: Discussionmentioning

confidence: 65%

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Prenatal diagnosis of feta noncompaction cardiomyopathy with de novo CALM2 mutation

zhang¹,

Dai

Liu³

et al. 2021

Preprint

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We report what apprears to be the first case of fetal noncompaction cardiomyopathy in both ventricles accompanied by a mutation in the calmodulin gene (CALM2): A 25-year-old woman was referred to our hospital at 25+1 weeks of gestation for evaluation of fetal defects. A postnatal echocardiography showed biventricular noncompaction cardiomyopathy. After terminated the pregnancy, fetal noncompaction cardiomyopathy was comfirmed by autopsy and histopathologic examination. And the whole-exome sequencing of genomic DNA demonstrated a de novo heterozygous mutation (c.389A>G;p.D130G) in CALM2, whereas the parents were normal. In this case report, we highlight the gene mutation in noncompaction cardiomyopathy.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 65%

Prenatal diagnosis of feta noncompaction cardiomyopathy with de novo CALM2 mutation

zhang¹,

Dai

Liu³

et al. 2021

Preprint

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“…The publicly open NIH program announcement (PA-19-034) detailing the classification and identification of 390 understudied druggable genomes was utilized to acquire the list of 261 candidate genes encoding GPCRs and ion channels. The associated literature survey was performed until 9 December 2021, with emphasis on published title words with (1) ion channels since 2017 [4,5,[9][10][11][12][13][14]16,26,27,30,33,[39][40][41][42]44,[46][47][48]53,54,59,61,[69][70][71][72][73][74][75][76][77][78][79][80], (2) ion channel blockers since 2017 [41,[81][82][83][84][85][86][87][88][89][90]…”

Section: Database Literature and Open-access Softwarementioning

confidence: 99%

“…Ion channels function as a gate via opening or closing by extracellular ligands [4], transmembrane voltage changes [5], or intracellular second messengers [6,7]. Mutations in ion channels are either causative or contributory to the pathogenesis of numerous disorders, such as cystic fibrosis [8,9], long-QT syndrome of the heart [10][11][12][13][14], heritable hypertension (e.g., Liddle's syndrome) [15][16][17][18], hyperinsulinemia and hypoglycemia of infancy [19][20][21], hereditary nephrolithiasis (e.g., Dent's disease) [22][23][24], and certain hereditary myopathies [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Drug-Targeted Genomes: Mutability of Ion Channels and GPCRs

et al. 2022

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Mutations of ion channels and G-protein-coupled receptors (GPCRs) are not uncommon and can lead to cardiovascular diseases. Given previously reported multiple factors associated with high mutation rates, we sorted the relative mutability of multiple human genes by (i) proximity to telomeres and/or (ii) high adenine and thymine (A+T) content. We extracted genomic information using the genome data viewer and examined the mutability of 118 ion channel and 143 GPCR genes based on their association with factors (i) and (ii). We then assessed these two factors with 31 genes encoding ion channels or GPCRs that are targeted by the United States Food and Drug Administration (FDA)-approved drugs. Out of the 118 ion channel genes studied, 80 met either factor (i) or (ii), resulting in a 68% match. In contrast, a 78% match was found for the 143 GPCR genes. We also found that the GPCR genes (n = 20) targeted by FDA-approved drugs have a relatively lower mutability than those genes encoding ion channels (n = 11), where targeted genes encoding GPCRs were shorter in length. The result of this study suggests that the use of matching rate analysis on factor-druggable genome is feasible to systematically compare the relative mutability of GPCRs and ion channels. The analysis on chromosomes by two factors identified a unique characteristic of GPCRs, which have a significant relationship between their nucleotide sizes and proximity to telomeres, unlike most genetic loci susceptible to human diseases.

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“…Three unrelated children aged 4 and 7 had LQTS and CPVT and carried the CALM2 p.Asn98Ser mutation13,31 . An 11-year-old girl who had a CALM2 p.Asp132Gly mutation was reported to suffer from LQTS, sinus bradycardia, and right bundle branch block36 . A 3-week-old baby girl who had a CALM2 p.Asp96Val mutation showed markedly prolonged QTc and cardiac arrest due to multiple episodes of ventricular fibrillation (VF)6 .…”

mentioning

confidence: 99%

Long QT syndrome: Identification of a novel de novo mutation of calmodulin in a newborn girl

Nguyen

Bui

Nguyen³

et al. 2022

Biomed. Res. Ther.

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Background: Long QT syndrome (LQTS) is a genetically and phenotypically heterogeneous disorder of ventricular myocardial repolarization that is typically characterized by prolongation of the heart rate-corrected QT interval on a 12-lead electrocardiogram (ECG). LQTS has a complicated etiology since great genotypic and phenotypic overlapping among LQTSs limits the establishment of a diagnosis based solely on clinical features. Case presentation: Here, we describe a Vietnamese newborn with a novel calmodulin (CALM2) variant. The patient was referred to the Department of Cardiology at Children's Hospital 2 in Ho Chi Minh City, Vietnam for multiple clinical cardiac presentations. The patient's family history was negative for cardiovascular diseases; however, she suffered from recurrent syncope and QT interval prolongation on resting in a 12-lead surface ECG. A fetal echocardiogram at 29 weeks detected signs of congenital heart disease. The newborn patient then suffered from sudden cardiac arrest and required cardiopulmonary resuscitation. Two weeks later, the patient suffered from torsade de pointes for the third time and required electrical shocks. An endotracheal tube was placed through the mouth into the trachea to facilitate breathing. Unfortunately, the patient expired at 3 months of age due to serious inflammatory issues. Whole exome sequencing (WES) -a technique used to determine variations in all coding regions (exons) of the known genes -validated a total of four rare variants in four cardiomyopathy (CM) genes, the CALM2, DSP, MYBPC3, and SPEG genes. We identified a novel de novo heterozygous missense mutation, c.280G > T (p.Asp94Tyr), in the CALM2 gene (NM_001305626) encoding calmodulin, which is a ubiquitous calcium-binding protein that is important for a myriad of intracellular signaling events of cardiac function. Conclusion: The results obtained in this study support the ``pan-cardiomyopathy panel'' approach, in which the molecular diagnosis of LQTS, the early identification of arrhythmia development, and the improved clinical management of cardiovascular disease patients are applied. Trial registration: The procedures were reviewed and approved by the Ethical Committee of the University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam, under the number UMP-VN 2018-10a12.

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Novel Association of a De Novo CALM2 Mutation With Long QT Syndrome and Hypertrophic Cardiomyopathy

Cited by 15 publications

References 5 publications

Prenatal diagnosis of feta noncompaction cardiomyopathy with de novo CALM2 mutation

Prenatal diagnosis of feta noncompaction cardiomyopathy with de novo CALM2 mutation

Drug-Targeted Genomes: Mutability of Ion Channels and GPCRs

Long QT syndrome: Identification of a novel de novo mutation of calmodulin in a newborn girl

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