Mutation site dependent variability of cardiac events in Japanese LQT2 form of congenital long-QT syndrome.
BACKGROUND
In the LQT2 form of long QT syndrome (LQTS), mutation sites are reported to correlate with clinical phenotypes in Caucasians, but the relationship in Asian patients remains unknown. The present study was designed to determine whether the location of KCNH2 mutations would influence the arrhythmic risk in LQT2 patients.


RESULTS
In 118 genetically-confirmed LQT2 patients (69 families, 62 KCNH2 mutations), the ECG parameters, Schwartz scores, and the incidence of cardiac events, defined as syncope, aborted cardiac arrest, and sudden cardiac death, were evaluated. To examine the effect of mutation sites, the participants were divided accordingly: pore (n=56) and non-pore (n=62) groups. The corrected QTend interval was significantly greater in the pore than in the non-pore group (QTc; 522+/-63 ms vs 490+/-49 ms, p=0.002). In this study, the clinical course of each of the probands did not differ according to the mutation sites, whereas non-probands carrying the pore site mutation experienced their first cardiac events at significantly younger age than those with the non-pore site mutation (log-rank, p=0.0005).


CONCLUSIONS
In a Japanese LQT2 cohort, family members with the pore site mutation were at higher arrhythmic risk than those with the non-pore site mutation.
Nagaoka
Iori
I
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.
Shimizu
Wataru
W
Itoh
Hideki
H
Yamamoto
Satoshi
S
Sakaguchi
Tomoko
T
Oka
Yuko
Y
Tsuji
Keiko
K
Ashihara
Takashi
T
Ito
Makoto
M
Yoshida
Hidetada
H
Ohno
Seiko
S
Makiyama
Takeru
T
Miyamoto
Yoshihiro
Y
Noda
Takashi
T
Kamakura
Shiro
S
Akao
Masaharu
M
Horie
Minoru
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D015331:Cohort Studies; D018572:Disease-Free Survival; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation; D006801:Humans; D008133:Long QT Syndrome / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012307:Risk Factors; D016171:Torsades de Pointes / Q000208:ethnology / Q000235:genetics
D018389:Codon, Nonsense