A homozygous SCN5A mutation in a severe, recessive type of cardiac conduction disease.
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A homozygous SCN5A mutation in a severe, recessive type of cardiac conduction disease. / Neu, Axel; Eiselt, Michele; Paul, Matthias; Sauter, Kathrin; Stallmeyer, Birgit; Isbrandt, Dirk; Schulze-Bahr, Eric.
In: HUM MUTAT, Vol. 31, No. 8, 8, 2010, p. 1609-1621.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - A homozygous SCN5A mutation in a severe, recessive type of cardiac conduction disease.
AU - Neu, Axel
AU - Eiselt, Michele
AU - Paul, Matthias
AU - Sauter, Kathrin
AU - Stallmeyer, Birgit
AU - Isbrandt, Dirk
AU - Schulze-Bahr, Eric
PY - 2010
Y1 - 2010
N2 - Cardiac sodium channels are key players in the generation and propagation of action potentials in the human heart. Heterozygous mutations in the SCN5A gene have been found to be associated with long QT syndrome, Brugada syndrome, and sinus node dysfunction (SND). Recently, overlapping arrhythmia phenotypes have been reported as well. Here we describe a novel recessive SCN5A mutation in a family originating from the German minority in White Russia. Four affected children with a history of early cardiac arrhythmia encompassing SND, conduction disease, and severe ventricular arrhythmias, are homozygous carriers of a novel SCN5A missense mutation (p.I230T) in the channel protein. Interestingly, the heterozygous mutation carriers had neither significant ECG abnormalities nor a history of cardiac events. Heterologous expression of SCN5A(I230T) channels revealed normal protein transport but altered biophysical sodium channel properties. Voltage range of both activation and inactivation were shifted in a way that resulted in decreased sodium current and loss of channel function. In conclusion, we describe a rare clinical condition with a novel SCN5A mutation causing a new type of complex cardiac arrhythmia. Unlike most previously reported sodium channelopathies, this overlap syndrome displays recessive inheritance characteristics and does not seem to follow simple Mendelian rules.
AB - Cardiac sodium channels are key players in the generation and propagation of action potentials in the human heart. Heterozygous mutations in the SCN5A gene have been found to be associated with long QT syndrome, Brugada syndrome, and sinus node dysfunction (SND). Recently, overlapping arrhythmia phenotypes have been reported as well. Here we describe a novel recessive SCN5A mutation in a family originating from the German minority in White Russia. Four affected children with a history of early cardiac arrhythmia encompassing SND, conduction disease, and severe ventricular arrhythmias, are homozygous carriers of a novel SCN5A missense mutation (p.I230T) in the channel protein. Interestingly, the heterozygous mutation carriers had neither significant ECG abnormalities nor a history of cardiac events. Heterologous expression of SCN5A(I230T) channels revealed normal protein transport but altered biophysical sodium channel properties. Voltage range of both activation and inactivation were shifted in a way that resulted in decreased sodium current and loss of channel function. In conclusion, we describe a rare clinical condition with a novel SCN5A mutation causing a new type of complex cardiac arrhythmia. Unlike most previously reported sodium channelopathies, this overlap syndrome displays recessive inheritance characteristics and does not seem to follow simple Mendelian rules.
M3 - SCORING: Zeitschriftenaufsatz
VL - 31
SP - 1609
EP - 1621
JO - HUM MUTAT
JF - HUM MUTAT
SN - 1059-7794
IS - 8
M1 - 8
ER -
