Clinical and Genetic Analysis of Long QT Syndrome in Children from Six Families in Saudi Arabia: Are They Different?

被引:11
作者
Bhuiyan, Zahurul A. [1 ]
Al-Shahrani, Safar
Al-Khadra, Ayman S. [3 ,5 ]
Al-Ghamdi, Saleh [2 ,4 ]
Al-Khalaf, Khalaf [4 ]
Mannens, Marcel M. A. M. [1 ]
Wilde, Arthur A. M.
Momenah, Tarek S. [4 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands
[2] Khamis Mashayt Mil Hosp, Dept Cardiol, Riyadh, Saudi Arabia
[3] Prince Sultan Cardiac Ctr, Dept Adult Cardiol, Riyadh, Saudi Arabia
[4] Prince Sultan Cardiac Ctr, Dept Pediat Cardiol, Riyadh, Saudi Arabia
[5] Univ Amsterdam, Acad Med Ctr, Heart Failure Res Ctr, NL-1105 AZ Amsterdam, Netherlands
关键词
Sudden cardiac death; Genetics; Long QT syndrome; Consanguinity; Founder mutation; POTASSIUM CHANNEL GENE; LANGE-NIELSEN-SYNDROME; ROMANO-WARD-SYNDROME; LATE SODIUM CURRENT; T-WAVE PATTERNS; CARDIAC-ARRHYTHMIA; I-KR; HEART-DISEASE; MUTATIONS; HERG;
D O I
10.1007/s00246-008-9377-y
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Congenital long QT syndrome (LQTS) is an inherited cardiac arrhythmia disorder characterized by prolongation of the QT interval; patients are predisposed to ventricular tachyarrhythmias and fibrillation leading to recurrent syncope or sudden cardiac death. We performed clinical and genetic studies in six Saudi Arabian families with a history of sudden unexplained death of children. Clinical symptoms, ECG phenotypes, and genetic findings led to the diagnosis of LQT1 in two families (recessive) and LQT2 in four families (three recessive and one dominant). Onset of arrhythmia was more severe in the recessive carriers and occurred during early childhood in all recessive LQT1 patients. Arrhythmia originated at the intrauterine stages of life in the recessive LQT2 patients. LQT1, causing mutation c.387-5 T > A in the KCNQ1 gene, and LQT2, causing mutation c.3208 C > T in the KCNH2 gene, are presumably founder mutations in the Assir province of Saudi Arabia. Further, all LQTS causing mutations detected in this study are novel and have not been reported in other populations.
引用
收藏
页码:490 / 501
页数:12
相关论文
共 49 条
[1]   Genetic dilsorders in the Arab world [J].
Al-Gazali, Lihadh ;
Hamamy, Hanan ;
Al-Arrayad, Shaikha .
BMJ-BRITISH MEDICAL JOURNAL, 2006, 333 (7573) :831-834B
[2]  
Bazett HC, 1920, HEART-J STUD CIRC, V7, P353
[3]  
BHUIYAN ZA, 2008, PROG BIOPHYS MOL BIO
[4]   Recurrent intrauterine fetal loss due to near absence of HERG: Clinical and functional characterization of a homozygous nonsense HERG Q1070X mutation [J].
Bhuiyan, Zahurul A. ;
Momenah, Tarek S. ;
Gong, Qiuming ;
Amin, Ahmad S. ;
Ghamdi, Saleh Al ;
Carvalho, Julene S. ;
Homfray, Tessa ;
Mannens, Marcel M. A. M. ;
Zhou, Zhengfeng ;
Wilde, Arthur A. M. .
HEART RHYTHM, 2008, 5 (04) :553-561
[5]   Mutation of an A-kinase-anchoring protein causes long-QT syndrome [J].
Chen, Lei ;
Marquardt, Michelle L. ;
Tester, David J. ;
Sampson, Kevin J. ;
Ackerman, Michael J. ;
Kass, Robert S. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (52) :20990-20995
[6]   Homozygous deletion in KVLQT1 associated with Jervell and Lange-Nielsen syndrome [J].
Chen, QY ;
Zhang, DM ;
Gingell, RL ;
Moss, AJ ;
Napolitano, C ;
Priori, SG ;
Schwartz, PJ ;
Kehoe, E ;
Robinson, JL ;
Schulze-Bahr, E ;
Wang, Q ;
Towbin, JA .
CIRCULATION, 1999, 99 (10) :1344-1347
[7]   C-terminal HERG (LQT2) mutations disrupt IKr channel regulation through 14-3-3ε [J].
Choe, Chi-un ;
Schulze-Bahr, Eric ;
Neu, Axel ;
Xu, Jun ;
Zhu, Zheng I. ;
Sauter, Kathrin ;
Bahring, Robert ;
Priori, Silvia ;
Guicheney, Pascale ;
Monnig, Gerold ;
Neapolitano, Carlo ;
Heidemann, Jan ;
Clancy, Colleen E. ;
Pongs, Olaf ;
Isbrandt, Dirk .
HUMAN MOLECULAR GENETICS, 2006, 15 (19) :2888-2902
[8]   Novel mechanism for sudden infant death syndrome: Persistent late sodium current secondary to mutations in caveolin-3 [J].
Cronk, Lisa B. ;
Ye, Bin ;
Kaku, Toshihiko ;
Tester, David J. ;
Vatta, Matteo ;
Makielski, Jonathan C. ;
Ackerman, Michael J. .
HEART RHYTHM, 2007, 4 (02) :161-166
[9]   KCNH2-K897T is a genetic modifier of latent congenital long-QT syndrome [J].
Crotti, L ;
Lundquist, AL ;
Insolia, R ;
Pedrazzini, M ;
Ferrandi, C ;
De Ferrari, GM ;
Vicentini, A ;
Yang, P ;
Roden, DM ;
George, AL ;
Schwartz, PJ .
CIRCULATION, 2005, 112 (09) :1251-1258
[10]  
CROTTI L, 2005, CIRCULATION S2, V112