1.Ion channelopathies and inherited arrhythmia.
Journal of Zhejiang University. Medical sciences 2010;39(1):97-102
Ion channelopathies are the mainly etiopathogenisis of inherited arrhythmia. Those arrhythmia syndromes are commonly caused by ion channel gene mutation, which can be classified as sodium,potassium and calcium ion channel mutation.Changes in the genes encoding for cardiac ion channel subunits produce modification in the function of the channels, and cause the dysfunctions of cardiac electrical activity; and the clinical manifestation is malignant arrhythmia.
Animals
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Arrhythmias, Cardiac
;
genetics
;
physiopathology
;
Channelopathies
;
genetics
;
physiopathology
;
Humans
;
Ion Channels
;
genetics
;
physiology
;
Mutation
2.Analysis of SCN4A gene variation in a Chinese pedigree affected with skeletal muscle sodium channelopathies.
Yan LU ; Xiaohui YANG ; Xiuxia WANG ; Ping XUE ; Jinhong ZHANG ; Yuejing LI
Chinese Journal of Medical Genetics 2019;36(8):809-812
OBJECTIVE:
To explore the clinical features of a Chinese pedigree affected with skeletal muscle sodium channelopathies due to variation of SCN4A gene.
METHODS:
Potential variation of the 24 exons of the SCN4A gene was screened using PCR and Sanger sequencing.
RESULTS:
Four family members were affected with the disease in an autosomal dominant inheritance pattern. Three patients had normekalemic periodic paralysis, while 1 showed paramyotonia congenita. Genetic analysis detected a missense variation c.2078T>C (p.Ile693Thr) in exon 13 of the SCN4A gene in the proband and other 3 affected relatives.
CONCLUSION
Normokalemic periodic paralysis and paramyotonia congenita can occur in different family members with skeletal muscle sodium channelopathies due to c.2078T>C(p.Ile693Thr) variation of SCN4A gene.
Channelopathies
;
genetics
;
Humans
;
Muscle, Skeletal
;
physiopathology
;
Mutation
;
NAV1.4 Voltage-Gated Sodium Channel
;
genetics
;
Pedigree
3.Research Progress and Forensic Application of Postmortem Genetic Testing in Hereditary Cardiac Diseases.
Yi-Ming DONG ; Chen-Teng YANG ; Guo-Zhong ZHANG ; Bin CONG
Journal of Forensic Medicine 2022;38(3):374-384
Hereditary cardiac disease accounts for a large proportion of sudden cardiac death (SCD) in young adults. Hereditary cardiac disease can be divided into hereditary structural heart disease and channelopathies. Hereditary structural heart disease mainly includes hereditary cardiomyopathy, which results in arhythmia, heart failure and SCD. The autopsy and histopathological examinations of SCD caused by channelopathies lack characteristic morphological manifestations. Therefore, how to determine the cause of death in the process of examination has become one of the urgent problems to be solved in forensic identification. Based on the review of recent domestic and foreign research results on channelopathies and hereditary cardiomyopathy, this paper systematically reviews the pathogenesis and molecular genetics of channelopathies and hereditary cardiomyopathy, and discusses the application of postmortem genetic testing in forensic identification, to provide reference for forensic pathology research and identification of SCD.
Autopsy/methods*
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Channelopathies/genetics*
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Death, Sudden, Cardiac/pathology*
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Genetic Testing
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Heart Diseases/genetics*
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Humans
;
Young Adult
4.Novel compound heterozygous SCN9A variations causing congenital insensitivity to pain in a patient.
Ying BAI ; Yue SUN ; Jing WU ; Ning LIU ; Zhihui JIAO ; Qianqian LI ; Kaihui ZHAO ; Xiangdong KONG
Chinese Journal of Medical Genetics 2022;39(4):392-396
OBJECTIVE:
To explore the genetic basis for a child featuring congenital insensitivity to pain (CIP).
METHODS:
Targeted capture and next generation sequencing (NGS) was carried out for the proband. Suspected pathogenic variants were confirmed by Sanger sequencing of the proband and his parents.
RESULTS:
The proband was found to harbor compound heterozygous variants of SCN9A gene, namely c.1598delA (p.N533Ifs*31) and c.295_296delCGinsAT (p.R99I), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic, and neither was reported previously.
CONCLUSION
The compound heterozygous variants of the SCN9A gene probably underlay the CIP in this child. Above finding has enabled genetic counseling for this family.
Channelopathies
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Child
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High-Throughput Nucleotide Sequencing
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Humans
;
Mutation
;
NAV1.7 Voltage-Gated Sodium Channel/genetics*
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Pain Insensitivity, Congenital/genetics*
5.Research Progress of the Correlation between Caveolin and Unexpected Sudden Cardiac Death.
Fang Yu WU ; Lian Lei GAI ; Xiao Ping KONG ; Bo HAO ; Er Wen HUANG ; He SHI ; Li Hui SHENG ; Li QUAN ; Shui Ping LIU ; Bin LUO
Journal of Forensic Medicine 2017;33(3):284-288
Due to the negative autopsy and without cardiac structural abnormalities, unexpected sudden cardiac death (USCD) is always a tough issue for forensic pathological expertise. USCD may be associated with parts of fatal arrhythmic diseases. These arrhythmic diseases may be caused by disorders of cardiac ion channels or channel-related proteins. Caveolin can combine with multiple myocardial ion channel proteins through its scaffolding regions and plays an important role in maintaining the depolarization and repolarization of cardiac action potential. When the structure and function of caveolin are affected by gene mutations or abnormal protein expression, the functions of the regulated ion channels are correspondingly impaired, which leads to the occurrence of multiple channelopathies, arrhythmia or even sudden cardiac death. It is important to study the effects of caveolin on the functions of ion channels for exploring the mechanisms of malignant arrhythmia and sudden cardiac death.
Arrhythmias, Cardiac/physiopathology*
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Autopsy
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Caveolins/metabolism*
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Channelopathies/genetics*
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Death, Sudden, Cardiac/pathology*
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Forensic Pathology
;
Humans
;
Ion Channels/metabolism*
;
Mutation
;
Myocardium
6.Current Issues in Migraine Genetics.
Journal of Clinical Neurology 2005;1(1):8-13
Migraine often runs in families and is associated with both genetic and environmental factors. Clinical and genetic heterogeneity as well as the influence of environmental factors have hampered the identification of the gene responsible for migraine disorder. Family/twin studies suggest the presence of hereditary susceptibility. Several different types of mutations or association studies with genetic polymorphism in neurotransmitters, inflammatory cytokines, homocysteine metabolism, mitochondria, or other risk genes in cerebrovascular disorders have been reported. Recently, progress of molecular genetics in familial hemiplegic migraine has provided important insights, a channelopathy, and now extending to a growing list of membrane excitability disorders. Further identification of candidate genes for migraine and exploring the correlation between phenotype and genotype are expected in the future for the understanding of migraine pathophysiology.
Cerebrovascular Disorders
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Channelopathies
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Cytokines
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Genetic Heterogeneity
;
Genetics*
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Genotype
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Homocysteine
;
Humans
;
Membranes
;
Metabolism
;
Migraine Disorders*
;
Migraine with Aura
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Mitochondria
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Molecular Biology
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Neurotransmitter Agents
;
Phenotype
;
Polymorphism, Genetic
7.Genetics of Channelopathy: Familial Periodic Paralysis.
Journal of the Korean Neurological Association 2005;23(6):737-744
Familial periodic paralysis (FPP) is inherited as a dominant trait, and the intermittent failure to maintain the skeletal muscle resting potential is due to mutations in the genes coding for the voltage-gated ion channels. Because several variants of FPP have been delineated on the bases of clinical features, the expectation was that these variants might be due to involvement of different classes of ion channels. The reality of the situation has proven to be more complicated. Mutation-induced defects in the same channel may give rise to diverse phenotypes (phenotypic heterogeneity) and, conversely, mutation in different channel genes may produce a common phenotype (genetic heterogeneity). Regardless of which type of ion channel is defective, the final common pathway is the depolarization-induced loss of muscle excitability; gain-of-function defect in voltage-gated Na channel may cause myotonia, periodic paralysis or both, clinical features of hyperkalemic periodic paralysis and paramyotonia congenita, and loss-of-function defects in voltage-gated Na and Ca channel and K channel may be responsible for periodic paralysis, cardiac arrhythmia or both in hypokalemic periodic paralysis or Andersen's syndrome, respectively. This review focuses on the clinical features, molecular genetic defects, and pathophysiologic mechanisms that underlie FPP.
Arrhythmias, Cardiac
;
Channelopathies*
;
Clinical Coding
;
Genetics*
;
Hypokalemic Periodic Paralysis
;
Ion Channels
;
Membrane Potentials
;
Molecular Biology
;
Muscle, Skeletal
;
Myotonia
;
Myotonic Disorders
;
Paralyses, Familial Periodic*
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Paralysis
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Paralysis, Hyperkalemic Periodic
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Phenotype
8.Postmortem genetic testing in sudden cardiac death due to ion channelopathies.
Journal of Forensic Medicine 2010;26(2):120-127
Sudden cardiac death accounts for majority of deaths in human. Evident cardiac lesions that may explain the cause of death can be detected in comprehensive postmortem investigation in most sudden cardiac death. However, no cardiac morphological abnormality is found in a considerable number of cases although the death is highly suspected from cardiac anomaly. With the advances in the modern molecular biology techniques, it has been discovered that many of these sudden deaths are caused by congenital ion channelopathies in myocardial cell, i.e., Brugada syndrome, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome, etc. This article presents the molecular genetics, electrocardiographic abnormalities, clinical manifestations, and mechanisms leading to sudden cardiac death with emphasis on the role of postmortem genetic testing in certification of cause of death. It may provide helpful information in investigating sudden cardiac death due to ion channelopathies in medico-legal practice.
Arrhythmias, Cardiac/genetics*
;
Autopsy/methods*
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Brugada Syndrome/genetics*
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Cause of Death
;
Channelopathies/genetics*
;
Death, Sudden, Cardiac/pathology*
;
Electrocardiography
;
Forensic Pathology
;
Genetic Testing
;
Heart Conduction System/physiopathology*
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Humans
;
Ion Channels/genetics*
;
Long QT Syndrome/genetics*
;
Mutation
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Tachycardia, Ventricular/genetics*
9.Clinical and molecular genetic analysis of a family with normokalemic periodic paralysis.
Cui-jie WEI ; Dong WANG ; Shuo WANG ; Hui JIAO ; Dao-jun HONG ; Li-hua PU ; Hui XIONG
Chinese Journal of Pediatrics 2013;51(1):47-51
OBJECTIVEPeriodic paralysis (PP) is one type of skeletal muscle channelopathies characterized by episodic attacks of weakness. It is usually classified into hyperkalemic periodic paralysis (HyperPP), hypokalemic periodic paralysis (HypoPP) and normokalemic periodic paralysis (NormoPP) based on the blood potassium levels. HypoPP is the most common type of these three and NormoPP is the rarest one. The aim of this study was to explore the clinical and genetic features of a Chinese family with normokalemic periodic paralysis (NormoKPP).
METHODClinical features of all patients in the family with NormoKPP were analyzed. Genomic DNA was extracted from peripheral blood leukocytes and amplified with PCR. We screened all 24 exons of SCN4A gene and then sequence analysis was performed in those who showed heteroduplex as compared with unaffected controls.
RESULT(1) Fifteen members of the family were clinically diagnosed NormoKPP, and their common features are: onset within infacy, episodic attacks of weakness, the blood potassium levels were within normal ranges, high sodium diet or large dosage of normal saline could attenuate the symptom. One muscle biopsy was performed and examination of light and electronic microscopy showed occasionally degenerating myofibers. (2) Gene of 12 patients were screened and confirmed mutations of SCN4A genes--c. 2111 T > C/p. Thr704Met.
CONCLUSIONThe study further defined the clinical features of patients with NormoKPP, and molecular genetic analysis found SCN4A gene c. 2111 T > C/p. Thr704Met point mutation contributed to the disease. In line with the autosomal dominant inheritance laws, this family can be diagnosed with periodic paralysis, and be provided with genetic counseling. And the study may also help the clinical diagnosis, guide treatment and genetic counseling of this rare disease in China.
Amino Acid Sequence ; Channelopathies ; diagnosis ; genetics ; pathology ; Child ; DNA Mutational Analysis ; Female ; Humans ; Male ; Muscle, Skeletal ; pathology ; physiopathology ; Mutation ; NAV1.4 Voltage-Gated Sodium Channel ; genetics ; Paralyses, Familial Periodic ; diagnosis ; genetics ; pathology ; Pedigree ; Polymerase Chain Reaction ; Potassium ; blood
10.Cardiac sodium channelopathy from bench to bedside.
Chinese Journal of Pediatrics 2013;51(11):874-877
Arrhythmias, Cardiac
;
diagnosis
;
genetics
;
pathology
;
Brugada Syndrome
;
diagnosis
;
genetics
;
pathology
;
Channelopathies
;
diagnosis
;
genetics
;
pathology
;
DNA Mutational Analysis
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Electrocardiography
;
Genetic Testing
;
Heart Conduction System
;
physiopathology
;
Humans
;
Infant
;
Long QT Syndrome
;
diagnosis
;
genetics
;
pathology
;
Muscle Proteins
;
genetics
;
Mutation
;
NAV1.5 Voltage-Gated Sodium Channel
;
genetics
;
Sodium Channels
;
genetics
;
Sudden Infant Death
;
etiology