OBJECTIVETo diagnose a Chinese benign familial neonatal convulsions (BFNC) family at the level of gene and investigate its molecular pathogenesis.

METHODSAll family members were studied by clinical examinations and linkage analysis. Mutation analysis of KCNQ2 gene was made by means of polymerase chain reaction (PCR)-direct sequencing and PCR-single strand conformation polymorphism (SSCP) in the proband, 16 family members and 72 unrelated normal individuals.

RESULTSLinkage analysis hinted the linkage of BFNC to KCNQ2, while the linkage to KCNQ3 was excluded. Mutation 1931delG of KCNQ2 gene was found in the proband by DNA-direct sequencing. The same SSCP variant as the proband's was showed in the rest affected members of this family but not in the unaffected members of this family and all of the 72 unrelated normal individuals.

CONCLUSION1931delG of KCNQ2 gene can cause BFNC in China and is novel mutation. The combination of linkage analysis and gene analysis is useful for gene diagnosis.

Epilepsy, Benign Neonatal ; genetics ; Female ; Genetic Linkage ; Humans ; Infant, Newborn ; KCNQ2 Potassium Channel ; KCNQ3 Potassium Channel ; Mutation ; Potassium Channels ; chemistry ; genetics ; Potassium Channels, Voltage-Gated

AIMTo study the mRNA expression changes in the brain of rats after middle cerebral artery occlusion.

METHODSMiddle cerebral artery occlusion was used to induce ischemia in rat brain. The mRNA expression of voltage-dependent potassium channel subtypes, including Kv1.4, Kv1.5, Kv2.1 and Kv4.2, were detected in rat hippocampus and cortex by RT-PCR.

RESULTSMiddle cerebral artery occlusion induced a significant neurological injury in rats. After ischemia 2 h, the mRNA of Kv1.4, Kv2.1 and Kv4.2 in hippocampus increased by 50%, 67% and 90% , respectively. And the mRNA of Kv1.4 and Kv4.2 maintained at a high level in hippocampus after ischemia 24 h. In cortex, the mRNA level of all the four subtypes were not changed significantly after ischemia 2 h, but the mRNA of Kv2.1 and Kv4.2 increased by 70% and 62% after ischemia 24 h, respectively.

CONCLUSIONThe mRNA expression levels of voltage-dependent potassium channels were up-regulated in rat hippocampus and cortex after middle cerebral artery occlusion.

Animals ; Brain ; metabolism ; Infarction, Middle Cerebral Artery ; metabolism ; Kv1.4 Potassium Channel ; biosynthesis ; genetics ; Kv1.5 Potassium Channel ; biosynthesis ; genetics ; Male ; Potassium Channels, Voltage-Gated ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; Shab Potassium Channels ; biosynthesis ; genetics ; Shal Potassium Channels ; biosynthesis ; genetics ; Up-Regulation

Epilepsy is one of the most common and debilitating neurological diseases that affects more than 40 million people worldwide. Genetic factors contribute to the pathogenesis of epilepsy. Molecular genetic studies have identified 15 disease-causing genes for epilepsy. The majority of the genes encode ion channels, including voltage-gated potassium channels KCNQ2 and KCNQ3, sodium channels SCN1A, SCN2A, and SCN1B, chloride channels CLCN2, and ligand-gated ion channels CHRNA4, CHRNB2, GABRG2, and GABRA1. Interestingly, non-ion channel genes have also been identified as epilepsy genes, and these genes include G-protein-coupled receptor MASS1/VLGR1, GM3 synthase, and proteins with unknown functions such as LGI1, NHLRC1, and EFHC1. These studies make genetic testing possible in some patients, and further characterization of the identified epilepsy genes may lead to the development of new drugs and new treatments for patients with epilepsy.
Chloride Channels ; genetics ; Epilepsies, Myoclonic ; genetics ; Epilepsy ; genetics ; Epilepsy, Absence ; genetics ; Humans ; KCNQ2 Potassium Channel ; genetics ; KCNQ3 Potassium Channel ; genetics ; NAV1.1 Voltage-Gated Sodium Channel ; NAV1.2 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins ; genetics ; Sodium Channels ; genetics

OBJECTIVETo determine mutations of two common potassium channel subunit genes KCNQ1, KCNH2 causing long QT syndrome (LQTS) in the Chinese.

METHODSThirty-one Chinese LQTS pedigrees were characterized for mutations in the two LQTS genes, KCNQ1 and KCNH2, by sequencing.

RESULTSTwo novel KCNQ1 mutations, S277L in the S5 domain and G306V in the channel pore, and two novel KCNH2 mutations, L413P in the transmembrane domain S1 and L559H in the transmembrane domain S5 were identified. The triggering factors for cardiac events developed in these mutation carriers included physical exercise and excitation. Mutation L413P in KCNH2 was associated with the notched T wave on ECGs. Mutation L559H in KCNH2 was associated with the typical bifid T wave on ECGs. Mutation S277L in KCNQ1 was associated with a high-amplitude T wave and G306V was associated with a low-amplitude T wave. Two likely polymorphisms, IVS11 + 18C > T in KCNQ1 and L520V in KCNH2 were also identified in two LQTS patients.

CONCLUSIONSThe mutation rates for both KCNQ1 (6.4%) and KCNH2 (6.4%) are lower in the Chinese population than those from North America or Europe.

Asian Continental Ancestry Group ; Cation Transport Proteins ; China ; DNA-Binding Proteins ; ERG1 Potassium Channel ; Ether-A-Go-Go Potassium Channels ; Female ; Humans ; KCNQ Potassium Channels ; KCNQ1 Potassium Channel ; Long QT Syndrome ; genetics ; Male ; Mutation ; Potassium Channels ; genetics ; Potassium Channels, Voltage-Gated ; Trans-Activators ; Transcriptional Regulator ERG

To investigate the electrophysiology mechanisms of new anxiolytic and antidepressant drug: 4-butyl-alpha-agarofuran (AF-5), patch clamp-recording was used to test the effects of AF-5 on voltage-dependent sodium currents, voltage-dependent potassium currents, L-type voltage-dependent calcium currents and GABA dependent Cl(-) currents in primary cultured rat cortical neurons. Effects of AF-5 on Kv2.1 currents, expressed stably in HEK293 cells, were also tested. Our results showed that, delayed rectifier potassium currents (I(K(DR, L-type voltage-dependent calcium currents (I(LC-ca)) in primary cultured rat cortical neurons and Kv2.1 currents in HEK293 cells were significantly inhibited by AF-5, with IC50 as 6.17, 4.4 and 5.29 micromol x L(-1) respectively. However, voltage-dependent sodium currents (I(Na)), GABA dependent Cl(-) currents and transient outward potassium currents (I(K(A)) in primary cultured rat cortical neurons were not significantly blocked by AF-5. Our results concluded that, blocked I(K(DR)) and I(L-Ca) currents may be one of the mechanisms of anxiolytic and antidepression actions of AF-5.
Animals ; Antidepressive Agents ; pharmacology ; Calcium Channels, L-Type ; drug effects ; Cells, Cultured ; Cerebral Cortex ; cytology ; Chloride Channels ; drug effects ; Delayed Rectifier Potassium Channels ; drug effects ; HEK293 Cells ; Humans ; Neurons ; cytology ; Patch-Clamp Techniques ; Potassium Channels, Voltage-Gated ; drug effects ; Rats ; Rats, Wistar ; Sesquiterpenes ; pharmacology ; Shab Potassium Channels ; drug effects ; Voltage-Gated Sodium Channels ; drug effects

OBJECTIVETo search for the mutations of potassium voltage-gated channel, KQT-like subfamily member 1(KCNQ1) gene in 31 Chinese long QT syndrome(LQTS) families.

METHODSDue to the genetic heterogeneity, the genotype of patients was first predicted based on the spectrum of ST-T-wave patterns on ECG. Ten of 31 probands were considered as LQT1. Then the mutation of KCNQ1 gene was screened by the polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) technique combined with DNA sequencing in all members of these 10 families. To avoid omitting some LQT1 patients without typical characteristics and also to do methodological comparison, the mutations of KCNQ1 gene on 16 exons were screened by PCR and direct DNA sequencing in the rest 21 non-LQT1 probands only. Co-segregation analysis was carried out after the finding of an abnormal sequence. In case that the abnormality existed in patients only, the test of such exon was performed in 50 irrelevant normal individuals.

RESULTSTwo missense mutations and three single nucleotide polymorphisms (SNPs) were found in the LQT1 predicted families. The two mutations were S277L (1 family) and G306V (1 family) in exon 5 and were not reported previously. Three polymorphisms were 435C-->T (7 families), 1632C-->A (1 family), and IVS1+9 C-->G (3 families). Only a splice mutation IVS1+5G-->A (2 families) and a polymorphism IVS10+18C-->T (1 family) were found in the non-LQT1 predicted probands. All three mutations were localized within the functional domain of KCNQ1 and were co-segregated with the disease, and were not found in 50 normal individuals.

CONCLUSIONTwo novel missense mutations, 1 splice mutation and four SNPs on KCNQ1 gene were found in the 31 LQTS families. Combined with ECG-based genotype prediction, PCR-SSCP could find most mutations on KCNQ1 and be a simple and economic method for screening LQTS.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Infant ; KCNQ Potassium Channels ; KCNQ1 Potassium Channel ; Long QT Syndrome ; genetics ; Male ; Middle Aged ; Mutation ; Potassium Channels ; genetics ; Potassium Channels, Voltage-Gated

Epilepsy is a group of disorders characterized by recurrent seizures. The etiologies of idiopathic epilepsy commonly have a genetic basis. Gene mutations causing several of the inherited epilepsies have been mapped. In this review, the authors summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, emphasizing how genetic defects may correlate with the pathophysiological mechanisms of brain hyperexcitability and gene defects can lead to epilepsy by altering multiple and diverse aspects of neuronal function.
Epilepsy ; genetics ; Humans ; KCNQ2 Potassium Channel ; Mutation ; NAV1.1 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins ; genetics ; Potassium Channels ; genetics ; Potassium Channels, Voltage-Gated ; Receptors, Nicotinic ; genetics ; Research ; trends ; Research Design ; Sodium Channels ; genetics ; Voltage-Gated Sodium Channel beta-1 Subunit

OBJECTIVE: To investigate KCNQ1, KCNH2, KCNE1 and KCNE2 gene variants in the cases of sudden manhood death syndrome (SMDS). METHODS: One hundred and sixteen sporadic cases of SMDS and one hundred and twenty-five healthy controlled samples were enrolled. Genomic DNA was extracted from blood samples. Gene variants of KCNQ1, KCNH2, KCNE1 and KCNE2 were screened by direct sequencing. RESULTS: A total of 14 mutations and 14 SNP were detected. Two non-synonymous mutations of them were newfound. There was no non-synonymous mutation found in the control group. CONCLUSION There are KCNQ1, KCNH2, KCNE1 and KCNE2 gene variants found in Chinese SMDS cases. KCNQ1, KCNH2, KCNE1 and KCNE2 gene mutation may correlate partly with the occurrence of some cases of the SMDS in China.
Base Sequence ; Case-Control Studies ; China ; DNA Mutational Analysis ; Death, Sudden/ethnology* ; ERG1 Potassium Channel ; Ether-A-Go-Go Potassium Channels/genetics* ; Humans ; KCNQ1 Potassium Channel/genetics* ; Long QT Syndrome ; Mutation ; Polymorphism, Single Nucleotide ; Potassium Channels ; Potassium Channels, Voltage-Gated/genetics*

AIMTo investigate mRNA expression changes of voltage-gated outward potassium channel subtypes in cultured rat hippocampal neurons after chronic exposure to beta-amyloid-petitde25-35 (beta-AP25-35).

METHODSmRNA expression was detected by RT-PCR, comparative expression levels were determined by imaging densitometer.

RESULTSDelayed rectifying (Kv2.1, Kv1.5), transient outward (Kv1.4, Kv4.2) and large conductance calcium-activated (rSlo) potassium channel mRNA were expressed in cultured rat hippocampal. In the presence of beta-AP25-35 3 mumol.L-1 for 24 h, the relative expression level of Kv2.1 was significantly increased (n = 3, P < 0.05); the other subtypes were not changed obviously (n = 3, P > 0.05). The increase of Kv2.1 mRNA mainly happened between 24 and 36 h after exposure to beta-AP25-35. After exposure to beta-AP25-35 for 60 h, Kv2.1 mRNA decreased significantly (n = 3, P < 0.01).

CONCLUSIONThe upregulation of Kv2.1 on transcription levels may be involved in the enhancement of delayed rectifying outward potassium (Ik) current induced by beta-AP25-35.

Amyloid beta-Peptides ; toxicity ; Animals ; Animals, Newborn ; Cell Division ; drug effects ; Cells, Cultured ; Delayed Rectifier Potassium Channels ; Female ; Gene Expression ; drug effects ; Hippocampus ; cytology ; Male ; Neurons ; drug effects ; metabolism ; Peptide Fragments ; toxicity ; Potassium Channels ; biosynthesis ; genetics ; Potassium Channels, Voltage-Gated ; RNA, Messenger ; biosynthesis ; drug effects ; Rats ; Rats, Wistar ; Shab Potassium Channels

The long QT syndrome (LQTS) is a rare hereditary disorder in which affected individuals have a possibility of ventricular tachyarrhythmia and sudden cardiac death. We investigated 62 LQTS (QTc > or = 0.47 sec) and 19 family members whose genetic study revealed mutation of LQT gene. In the proband group, the modes of presentation were ECG abnormality (38.7%), aborted cardiac arrest (24.2%), and syncope or seizure (19.4%). Median age of initial symptom development was 10.5 yr. Genetic studies were performed in 61; and mutations were found in 40 cases (KCNQ1 in 19, KCNH2 in 10, SCN5A in 7, KCNJ2 in 3, and CACNA1C in 1). In the family group, the penetrance of LQT gene mutation was 57.9%. QTc was longer as patients had the history of syncope (P = 0.001), ventricular tachycardia (P = 0.017) and aborted arrest (P = 0.010). QTc longer than 0.508 sec could be a cut-off value for major cardiac events (sensitivity 0.806, specificity 0.600). Beta-blocker was frequently applied for treatment and had significant effects on reducing QTc (P = 0.007). Implantable cardioverter defibrillators were applied in 6 patients. Congenital LQTS is a potentially lethal disease. It shows various genetic mutations with low penetrance in Korean patients.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/genetics ; Calcium Channels/genetics ; Child ; Child, Preschool ; Electrocardiography ; Heart Arrest/genetics/pathology ; Humans ; Infant ; KCNQ1 Potassium Channel/genetics ; KCNQ2 Potassium Channel/genetics ; Long QT Syndrome/*diagnosis/*genetics ; Middle Aged ; Mutation/*genetics ; NAV1.5 Voltage-Gated Sodium Channel/genetics ; Penetrance ; Potassium Channels, Inwardly Rectifying/genetics ; Republic of Korea ; Risk Factors ; Seizures/genetics/pathology ; Young Adult