当前位置： SCI文献检索 > Journal of Cardiology期刊下所有文献 > Novel KCNQ1 splicing mutation in patients with forme fruste LQT1 aggravated by hypokalemia.

Novel KCNQ1 splicing mutation in patients with forme fruste LQT1 aggravated by hypokalemia.

Abstract：

BACKGROUND:Several KCNQ1 splicing mutations have been identified in patients with type-1 long QT syndrome (LQT1). It was suggested that the clinical severity may differ according to the aberrant splicing products. There may be precipitating factors that cause cardiac events in those with a mild clinical phenotype (forme fruste LQT1). METHODS AND RESULTS:We analyzed the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes in 31 consecutive LQTS patients. A novel KCNQ1 1251+1G>A (IVS9+1G>A) mutation was identified in three probands and their two relatives. The QT interval in all of the five individuals with mutation was not much prolonged in the absence of precipitating factors (mean QTc was 461±30ms.). Two of the five individuals with mutation were symptomatic. One patient (a 38-year-old female) had experienced recurrent episodes of syncope due to ventricular tachyarrhythmias (VTAs) accompanied by QT prolongation (QTc: 750ms) when the serum potassium concentration ([K(+)]) was 2.7mEq/L. After correction of [K(+)], the QTc interval was shortened to 515ms, and the occurrence of VTAs ceased. Another patient (a 22-year-old female) was resuscitated from cardio-pulmonary arrest due to VTAs. Just after resuscitation, the QTc interval was 629ms, and [K(+)] was 2.9mEq/L. After correction of [K(+)], the QTc interval was dramatically shortened to 440ms. In order to identify abnormal splicing products of the responsible mutation, we analyzed the reverse transcription-polymerase chain reaction products from peripheral bloods of the mutation carrier, and identified exon 9-skipping (Δ9) and cryptic sequential exons 8 and 9-skipping (Δ8-9) products, as well as a no exon-skipping product. CONCLUSIONS:We identified a novel KCNQ splicing mutation 1251+1G>A in forme fruste LQT1, which induces cryptic splicing. Two of the five individuals with mutation experienced VTAs in the setting of hypokalemia, emphasizing the need to increase awareness of the significance of hypokalemia in this subgroup of LQT1 patients.

journal_name

J Cardiol

journal_title

Journal of cardiology

authors

Imai M,Nakajima T,Kaneko Y,Niwamae N,Irie T,Ota M,Iijima T,Tange S,Kurabayashi M

doi

10.1016/j.jjcc.2013.11.014

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

121-6

issue

eissn

0914-5087

issn

1876-4738

pii

S0914-5087(13)00370-5

journal_volume

pub_type

杂志文章

在线工具

Novel KCNQ1 splicing mutation in patients with forme fruste LQT1 aggravated by hypokalemia.