Case Report: Biventricular Noncompaction Cardiomyopathy With Pulmonary Stenosis and Bradycardia in a Fetus With KCNH2 Mutation

Sun, Hairui; Liu, Xiaowei; Hao, Xiaoyan; Zhou, Xiaoxue; Wang, Jingyi; Han, Jiancheng; Liang, Mengmeng; Zhang, Hongjia; He, Yihua

doi:10.3389/fgene.2022.821226

Cited by 4 publications

(1 citation statement)

References 36 publications

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“…As a rare genetic cardiomyopathy, NCCM is regulated by various genes that are involved in encoding ion channels, sarcomeres, and chaperone proteins. The related ion channel genes mainly include SCN5A , RYR2 , KCNQ1 , and HCN4 ( 3 ). However, involvement of the calmodulin gene ( CALM2 ) in fetal NCCM has been rarely reported.…”

Section: Introductionmentioning

confidence: 99%

Case report: Prenatal diagnosis of fetal non-compaction cardiomyopathy with bradycardia accompanied by de novo CALM2 mutation

et al. 2022

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We herein report what appears to be the first case of fetal non-compaction 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. Prenatal echocardiography showed biventricular non-compaction cardiomyopathy with sinus bradycardia. After termination of the pregnancy, fetal biventricular non-compaction cardiomyopathy was confirmed by autopsy and histopathologic examination. Additionally, 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 importance of prenatal ultrasound and genetic testing in fetal non-compaction cardiomyopathy with arrhythmia.

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Section: Introductionmentioning

confidence: 99%

Case report: Prenatal diagnosis of fetal non-compaction cardiomyopathy with bradycardia accompanied by de novo CALM2 mutation

et al. 2022

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Very important pharmacogenetic variants landscape and potential clinical relevance in the Zhuang population from Yunnan province

Li,

Chang,

Yan

et al. 2024

Sci Rep

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The gradual evolution of pharmacogenomics has shed light on the genetic basis for inter-individual drug response variations across diverse populations. This study aimed to identify pharmacogenomic variants that differ in Zhuang population compared with other populations and investigate their potential clinical relevance in gene-drug and genotypic-phenotypic associations. A total of 48 variants from 24 genes were genotyped in 200 Zhuang subjects using the Agena MassARRAY platform. The allele frequencies and genotype distribution data of 26 populations were obtained from the 1000 Genomes Project, followed by a comparison and statistical analysis. After Bonferroni correction, significant differences in genotype frequencies were observed of CYP3A5 (rs776746), ACE (rs4291), KCNH2 (rs1805123), and CYP2D6 (rs1065852) between the Zhuang population and the other 26 populations. It was also found that the Chinese Dai in Xishuangbanna, China, Han Chinese in Beijing, China, and Southern Han Chinese, China showed least deviation from the Zhuang population. The Esan in Nigeria, Gambian in Western Division, The Gambia, and Yoruba in Ibadan, Nigeria exhibited the largest differences. This was also proved by structural analysis, Fst analysis and phylogenetic tree. Furthermore, these differential variants may be associated with the pharmacological efficacy and toxicity of Captopril, Amlodipine, Lisinopril, metoclopramide, and alpha-hydroxymetoprolol in the Zhuang population. Our study has filled the gap of pharmacogenomic information in the Zhuang population and has provided a theoretical framework for the secure administration of drugs in the Zhuang population.

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Functional Characterization of the A414G Loss-of-Function Mutation in HCN4 Associated with Sinus Bradycardia

Verkerk

Wilders

2023

Cardiogenetics

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Patients carrying the heterozygous A414G mutation in the HCN4 gene, which encodes the HCN4 protein, demonstrate moderate to severe bradycardia of the heart. Tetramers of HCN4 subunits compose the ion channels in the sinus node that carry the hyperpolarization-activated ‘funny’ current (If), also named the ‘pacemaker current’. If plays an essential modulating role in sinus node pacemaker activity. To assess the mechanism by which the A414G mutation results in sinus bradycardia, we first performed voltage clamp measurements on wild-type (WT) and heterozygous mutant HCN4 channels expressed in Chinese hamster ovary (CHO) cells. These experiments were performed at physiological temperature using the amphotericin-perforated patch-clamp technique. Next, we applied the experimentally observed mutation-induced changes in the HCN4 current of the CHO cells to If of the single human sinus node cell model developed by Fabbri and coworkers. The half-maximal activation voltage V1/2 of the heterozygous mutant HCN4 current was 19.9 mV more negative than that of the WT HCN4 current (p < 0.001). In addition, the voltage dependence of the heterozygous mutant HCN4 current (de)activation time constant showed a −11.9 mV shift (p < 0.001) compared to the WT HCN4 current. The fully-activated current density, the slope factor of the activation curve, and the reversal potential were not significantly affected by the heterozygous A414G mutation. In the human sinus node computer model, the cycle length was substantially increased, almost entirely due to the shift in the voltage dependence of steady-state activation, and this increase was more prominent under vagal tone. The introduction of a passive atrial load into the model sinus node cell further reduced the beating rate, demonstrating that the bradycardia of the sinus node was even more pronounced by interactions between the sinus node and atria. In conclusion, the experimentally identified A414G-induced changes in If can explain the clinically observed sinus bradycardia in patients carrying the A414G HCN4 gene mutation.

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Case Report: Biventricular Noncompaction Cardiomyopathy With Pulmonary Stenosis and Bradycardia in a Fetus With KCNH2 Mutation

Cited by 4 publications

References 36 publications

Case report: Prenatal diagnosis of fetal non-compaction cardiomyopathy with bradycardia accompanied by de novo CALM2 mutation

Case report: Prenatal diagnosis of fetal non-compaction cardiomyopathy with bradycardia accompanied by de novo CALM2 mutation

Very important pharmacogenetic variants landscape and potential clinical relevance in the Zhuang population from Yunnan province

Functional Characterization of the A414G Loss-of-Function Mutation in HCN4 Associated with Sinus Bradycardia

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