RESUMEN
OBJECTIVE: This study was performed to identify a possible relationship between genotype and phenotype in the congenital familial long QT syndrome (cLQTS). BACKGROUND: The cLQTS, which occurs as an autosomal dominant or recessive trait, is characterized by QT-interval prolongation on the electrocardiogram and torsade de pointes arrhythmias, which may give rise to recurrent syncope or sudden cardiac death. Precipitators for cardiac events are exercise or emotion and occasionally acoustic stimuli. METHODS: The trigger for cardiac events (syncope, documented cardiac arrhythmias, sudden cardiac death) was analyzed in 11 families with a familial LQTS and a determined genotype. RESULTS: The families were subdivided in KVLQT1-related families (LQTS1, n = 5) and HERG (human ether-a-gogo-related gene)-related families (LQTS2, n = 6) based on single-strand conformation polymorphism analysis and sequencing. Whereas exercise-related cardiac events dominate the clinical picture of LQTS1 patients, auditory stimuli as a trigger for arrhythmic events were only seen in LQTS2 patients. CONCLUSIONS: Arrhythmic events triggered by auditory stimuli may differentiate LQTS2 from LQTS1 patients.
Asunto(s)
Estimulación Acústica , Proteínas de Transporte de Catión , Proteínas de Unión al ADN , Síndrome de QT Prolongado/diagnóstico , Canales de Potasio con Entrada de Voltaje , Canales de Potasio/genética , Transactivadores , Adulto , Anciano , Anciano de 80 o más Años , ADN/análisis , Sondas de ADN/química , Muerte Súbita Cardíaca/etiología , Progresión de la Enfermedad , Canal de Potasio ERG1 , Electrocardiografía , Canales de Potasio Éter-A-Go-Go , Femenino , Estudios de Seguimiento , Genotipo , Frecuencia Cardíaca , Humanos , Canales de Potasio KCNQ , Canal de Potasio KCNQ1 , Síndrome de QT Prolongado/etiología , Síndrome de QT Prolongado/genética , Masculino , Mutación , Fenotipo , Polimorfismo Conformacional Retorcido-Simple , Regulador Transcripcional ERGRESUMEN
The human gene for the 10-kDa flavoprotein subunit of the mitochondrial NADH:ubiquinone oxidoreductase (Complex I) was completely cloned and sequenced. The so-called NDUFV3 gene contains three exons, spanning 20 kb. The open reading frame contains a 34-codon import sequence and a 74-codon mature protein sequence. A database search revealed close homology to bovine and rat protein sequence but not to any other known protein. Northern blot analysis showed that the NDUFV3 gene is ubiquitously expressed. The NDUFV3 gene was assigned by FISH to a single location on chromosome 21q22.3 and might contribute to the Down syndrome phenotype.