A novel SCN5A mutation associated with the linker between III and IV domains of Nav1.5 in a neonate with fatal long QT syndrome.
A male newborn weighing 2334 g was delivered at 37 weeks of gestation by caesarean section because of prenatal ultrasound findings of fetal hydrops with atrioventricualr block, ventriucular tachycardia (VT), and impaired ventricular function. In spite of the intravenous administration of lidocaine, VT continued. He developed poor perfusion and systemic hypotension. After the intravenous administration of amiodarone, VT was terminated. The electrocardiogram revealed an extremely prolonged corrected QT interval (860 ms) with 2:1 atrioventricular block. Unfortunately, he died 18 h after birth in spite of the administration of lidocaine, beta-blocker and magnesium. Mutational analysis identified a novel heterozygous de novo mutation (F1486del) in SCN5A. This mutation is associated with the IFM motif in the linker between III and IV domains of Na(v)1.5, which serves as an inactivation particle binding within the pore of sodium channels. This report demonstrates an interesting relationship between the clinical phenotype and the location of the mutation in long QT syndrome.
Yamamura
Kenichiro
K
Muneuchi
Jun
J
Uike
Kiyoshi
K
Ikeda
Kazuyuki
K
Inoue
Hirosuke
H
Takahata
Yasushi
Y
Shiokawa
Yuichi
Y
Yoshikane
Yukako
Y
Makiyama
Takeru
T
Horie
Minoru
M
Hara
Toshiro
T
D017809:Fatal Outcome; D017353:Gene Deletion; D006801:Humans; D007231:Infant, Newborn; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics*
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels