RESUMEN
<p><b>OBJECTIVE</b>To analyze the gene mutations on the cardiac sodium channel gene SCN5A in a Chinese family with Brugada syndrome.</p><p><b>METHOD</b>Polymerase chain reaction and DNA sequencing were used to screen gene mutations on the cardiac sodium channel gene SCN5A in all family members of a Chinese pedigree with Brugada syndrome, single strand conformation polymorphism analysis were performed in 136 normal controls to detect the mutations of SCN5A gene.</p><p><b>RESULT</b>Two heterozygosis mutations, which include a missense mutation (Y1494N) and a same sense mutation (A29A), were identified on SCN5A gene in the proband with Brugada syndrome and these mutations were not detected in other family members with Brugada syndrome and in controls.</p><p><b>CONCLUSION</b>We detected a reported polymorphism site (A29A) and a novel missense mutation (Y1494N) on SCN5A in this Chinese family with Brugada syndrome.</p>
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Pueblo Asiatico , Genética , Síndrome de Brugada , Genética , Estudios de Casos y Controles , Proteínas Musculares , Genética , Mutación , Linaje , Polimorfismo Conformacional Retorcido-Simple , Canales de Sodio , GenéticaRESUMEN
<p><b>OBJECTIVE</b>To explore the mutations of MEF2A gene in Chinese patients with coronary artery disease(CAD).</p><p><b>METHODS</b>With polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA direct sequencing, the mutation analysis of exon 11 of MEF2A gene was performed to 156 patients with CAD and 93 normal controls.</p><p><b>RESULTS</b>By DNA sequence analyzing the samples of abnormal mobility shift of SSCP, the MEF2A gene mutations were found in three patients with CAD. One of mutations was 147130(C>A)(P431Q), and the second one was 21 bases deletion(147108-147128) which was leading to the absence of 7 amino acids (424QQQQQQQ430), and the third was 147191(G>T). Three mutations were all found in one patient, but meanwhile 21 bases deletion was found in the other two patients.</p><p><b>CONCLUSION</b>Mutations in exon 11 of MEF2A gene exist in the patients with CAD, and the mutations may be pathological.</p>
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pueblo Asiatico , Genética , Secuencia de Bases , China , Enfermedad de la Arteria Coronaria , Etnología , Genética , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Genética , Factores de Transcripción MEF2 , Datos de Secuencia Molecular , Mutación , Factores Reguladores Miogénicos , Genética , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
<p><b>OBJECTIVE</b>To identify the mutation of a Chinese family with inherited long QT syndrome(LQTS).</p><p><b>METHODS</b>The disease-causing gene was tentatively determined in light of the clinical manifestations and electrophysiological properties, and then polymerase chain reaction and DNA sequencing were used for screening and identifying mutation.</p><p><b>RESULTS</b>A missense mutation G940A(G314S) in the KCNQ1 gene was identified, which was the 'hot spot' of long QT syndrome mutation.</p><p><b>CONCLUSION</b>The mutation that is involved with long QT syndrome in Chinese patients is the same as that in the European, American and Japanese patients.</p>
Asunto(s)
Femenino , Humanos , Masculino , China , Análisis Mutacional de ADN , Salud de la Familia , Predisposición Genética a la Enfermedad , Genética , Genotipo , Canal de Potasio KCNQ1 , Genética , Síndrome de QT Prolongado , Diagnóstico , Genética , Mutación Missense , Linaje , Reacción en Cadena de la PolimerasaRESUMEN
<p><b>OBJECTIVE</b>To investigate the molecular pathology in families with long QT syndrome (LQTS) including Jervell-Longe-Nielsen syndrome (JLNS) and Romano-ward syndrome (RWS) and Brugada syndrome (BS) in Chinese population.</p><p><b>METHODS</b>Polymerase chain reaction and DNA sequencing were used to screen for KCNQ1, KCNH2, KCNE1, and SCN5A mutation.</p><p><b>RESULTS</b>We identified a novel mutation N1774S in the SCN5A gene of the BS family, a novel mutation G314S in a RWS family which had also been found in Europe, North America, and Japan, and a single nucleotide polymorphisms (SNPs) G643S in the KCNQ1 of the JLNS family. In this JLNS family, another heterozygous novel mutation in exon 2a was found in KCNQ1 of the patients.</p><p><b>CONCLUSION</b>New mutations were found in our experiment, which expand the spectrum of KCNQ1 and SCN5A mutations that cause LQTS and BS.</p>
Asunto(s)
Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Secuencia de Bases , Canal de Potasio ERG1 , Canales de Potasio Éter-A-Go-Go , Genética , Síndrome de Jervell-Lange Nielsen , Genética , Canal de Potasio KCNQ1 , Genética , Síndrome de QT Prolongado , Genética , Datos de Secuencia Molecular , Proteínas Musculares , Genética , Mutación , Linaje , Canales de Potasio con Entrada de Voltaje , Genética , Síndrome de Romano-Ward , Genética , Canales de Sodio , GenéticaRESUMEN
We studied the effects of Chinese traditional medicine rhynchophylline (Rhy) on human ether-a-go-go related gene (HERG) channel and characterized the electrophysiological properties of Rhy's pharmacological effect on HERG channel using Xenopus oocytes. Xenopus oocytes were injected with either 23 nl (5.75 ng) HERG cRNA or 23 nl distilled water. Xenopus oocytes were randomly assigned to receive one of the following different concentrations of Rhy: (1) control, (2)10 mumol/L Rhy, (3)100 mumol/L Rhy, (4) 500 mumol/L Rhy, (5) 1 000 mumol/L Rhy, (6) 10 000 mumol/L Rhy. Cell currents were recorded in oocytes. The peak tail currents of HERG channel were inhibited by Rhy. The inhibition was in a dose-dependent manner [IC(50)=(773.4 +/- 42.5) mumol/L]. Experiment with 100 mumol/L Rhy indicated that the degree of HERG blockade showed some voltage dependence (within -40 mV to -20 mV ). Kinetic analyses revealed that Rhy decreased the rate of channel activation. The findings indicate that Rhy inhibits HERG encoded potassium channels. It may underline the molecular mechanism of myocardial electrophysiological characteristics associated with this drug.