TY - JOUR
T1 - Long QT syndrome, cardiovascular anomaly and findings in ECG-guided genetic testing
AU - Al Senaidi, Khalfan S.
AU - Wang, Guoliang
AU - Zhang, Li
AU - Beer, Dominik A.
AU - AlFarqani, Abdullah M.
AU - AlMaskaryi, Salim N.
AU - Penny, Daniel J.
AU - Kowey, Peter R.
AU - Fan, Yuxin
N1 - Publisher Copyright:
© 2014 The Authors. Published by Elsevier Ireland Ltd.
PY - 2014
Y1 - 2014
N2 - Objective: Patients with inherited long QT syndrome (LQTS) are prone to torsade de pointes and sudden death (SD). Identifying affected individuals is important for SD prevention. This study aimed to determine the cause and genotype-phenotype characteristics of LQTS in a large Omani family. Methods: Upon LQTS diagnosis of a 5-year-old girl (proband), targeted mutation screening was performed based on the gene-specific ECG pattern identified in her mother. ECG-guided family genotyping was conducted for identifying additional affected individuals. Results: ECGs of the proband demonstrated 2:1 AV block, incomplete right bundle branch block (IRBBB) and markedly prolonged QTc (571-638. ms) with bizarre T waves. Cardiac imaging revealed dilatation of the ascending aorta and pulmonary artery, and left ventricular non-compaction. Her parents were first cousins. Both showed mild QT prolongation, with the mother presenting a LQT2 T wave pattern and the father IRBBB. Targeted KCNH2 screening identified a novel homozygous frameshift mutation p.T1019Pfs. ×. 38 in the proband within 3 days. Family genotyping uncovered 3 concealed LQT2 and confirmed 11 members showing LQT2 ECG patterns as heterozygous mutation carriers. All heterozygous carriers were asymptomatic, with 71% showing normal to borderline prolonged QTc (458. ±. 33. ms, range 409-522. ms). Conclusion: p.T1019Pfs. ×. 38, a novel KCNH2 mutation, has been identified in a large LQTS family in Oman. Consanguineous marriages resulted in a homozygous with severe LQTS. ECG-guided phenotyping and genotyping achieved a high efficiency. Genetic testing is essential in identifying concealed LQTS. Further investigation is warranted to determine if there is a causative relationship between homozygous p.T1019Pfs. ×. 38 and cardiovascular anomaly.
AB - Objective: Patients with inherited long QT syndrome (LQTS) are prone to torsade de pointes and sudden death (SD). Identifying affected individuals is important for SD prevention. This study aimed to determine the cause and genotype-phenotype characteristics of LQTS in a large Omani family. Methods: Upon LQTS diagnosis of a 5-year-old girl (proband), targeted mutation screening was performed based on the gene-specific ECG pattern identified in her mother. ECG-guided family genotyping was conducted for identifying additional affected individuals. Results: ECGs of the proband demonstrated 2:1 AV block, incomplete right bundle branch block (IRBBB) and markedly prolonged QTc (571-638. ms) with bizarre T waves. Cardiac imaging revealed dilatation of the ascending aorta and pulmonary artery, and left ventricular non-compaction. Her parents were first cousins. Both showed mild QT prolongation, with the mother presenting a LQT2 T wave pattern and the father IRBBB. Targeted KCNH2 screening identified a novel homozygous frameshift mutation p.T1019Pfs. ×. 38 in the proband within 3 days. Family genotyping uncovered 3 concealed LQT2 and confirmed 11 members showing LQT2 ECG patterns as heterozygous mutation carriers. All heterozygous carriers were asymptomatic, with 71% showing normal to borderline prolonged QTc (458. ±. 33. ms, range 409-522. ms). Conclusion: p.T1019Pfs. ×. 38, a novel KCNH2 mutation, has been identified in a large LQTS family in Oman. Consanguineous marriages resulted in a homozygous with severe LQTS. ECG-guided phenotyping and genotyping achieved a high efficiency. Genetic testing is essential in identifying concealed LQTS. Further investigation is warranted to determine if there is a causative relationship between homozygous p.T1019Pfs. ×. 38 and cardiovascular anomaly.
KW - Gene-specific ECG patterns
KW - Heterozygous
KW - Homozygous
KW - Long QT syndrome
KW - Sudden death
UR - http://www.scopus.com/inward/record.url?scp=84922243891&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922243891&partnerID=8YFLogxK
U2 - 10.1016/j.ijchv.2014.06.001
DO - 10.1016/j.ijchv.2014.06.001
M3 - Article
AN - SCOPUS:84922243891
SN - 2214-7632
VL - 4
SP - 122
EP - 128
JO - IJC Heart and Vessels
JF - IJC Heart and Vessels
IS - 1
ER -