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Your search keyword '"Oberti C"' showing total 3 results
Start Over Author "Oberti C" Topic long qt syndrome
3 results on '"Oberti C"'

1. Protective effect of KCNH2 single nucleotide polymorphism K897T in LQTS families and identification of novel KCNQ1 and KCNH2 mutations.

Author

Zhang X, Chen S, Zhang L, Liu M, Redfearn S, Bryant RM, Oberti C, Vincent GM, and Wang QK

Subjects
Adolescent, Adult, Aged, Child, Cohort Studies, DNA Mutational Analysis, ERG1 Potassium Channel, Female, Genetic Linkage, Humans, Male, Middle Aged, Polymorphism, Single-Stranded Conformational, Ether-A-Go-Go Potassium Channels genetics, KCNQ1 Potassium Channel genetics, Long QT Syndrome genetics, Mutation, Polymorphism, Single Nucleotide
Abstract

Background: KCNQ1 and KCNH2 are the two most common potassium channel genes causing long QT syndrome (LQTS), an inherited cardiac arrhythmia featured by QT prolongation and increased risks of developing torsade de pointes and sudden death. To investigate the disease expressivity, this study aimed to identify mutations and common variants that can modify LQTS phenotype., Methods: In this study, a cohort of 112 LQTS families were investigated. Among them two large LQTS families linkage analysis with markers spanning known LQTS genes was carried out to identify the specific gene for mutational analysis. All exons and exon-intron boundaries of KCNH2 and KCNQ1 were sequenced for mutational analysis., Results: LQTS-associated mutations were identified in eight of 112 families. Two novel mutations, L187P in KCNQ1 and 2020insAG in KCNH2, were identified. Furthermore, in another LQTS family we found that KCNH2 mutation A490T co-segregated with a common SNP K897T in KCNH2. KCNH2 SNP K897T was reported to exert a modifying effect on QTc, but it remains controversial whether it confers a risk or protective effect. Notably, we have found that SNP K897T interacts with mutation A490T in cis orientation. Seven carriers for A490T and the minor allele T of SNP K897T showed shorter QTc and fewer symptoms than carriers with A490T or A490P (P < 0.0001)., Conclusion: Our family-based approach provides support that KCNH2 SNP K897T confers a protective effect on LQTS patients. Our study is the first to investigate the effect of SNP K897T on another KCNH2 mutation located in cis orientation. Together, our results expand the mutational and clinical spectrum of LQTS and provide insights into the factors that determine QT prolongation associated with increased risk of ventricular tachycardia and sudden death.

Published
2008
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2. KCNE1 mutations cause jervell and Lange-Nielsen syndrome.

Author

Schulze-Bahr E, Wang Q, Wedekind H, Haverkamp W, Chen Q, Sun Y, Rubie C, Hördt M, Towbin JA, Borggrefe M, Assmann G, Qu X, Somberg JC, Breithardt G, Oberti C, and Funke H

Subjects
Female, Gene Frequency, Genetic Markers, Heterozygote, Humans, Male, Microsatellite Repeats, Pedigree, Polymorphism, Genetic, Potassium Channels metabolism, Long QT Syndrome genetics, Mutation, Potassium Channels genetics, Potassium Channels, Voltage-Gated
Published
1997
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3. KCNQ1 mutations in patients with a family history of lethal cardiac arrhythmias and sudden death

Author

Chen, S, Zhang, L, Bryant, RM, Vincent, GM, Flippin, M, Lee, JC, Brown, E, Zimmerman, F, Rozich, R, Szafranski, P, Oberti, C, Sterba, R, Marangi, D, Tchou, PJ, Chung, MK, and Wang, Q

Subjects
Male, congenital, hereditary, and neonatal diseases and abnormalities, Potassium Channels, Base Sequence, KCNQ Potassium Channels, Molecular Sequence Data, Arrhythmias, Cardiac, Article, Pedigree, Electrocardiography, Long QT Syndrome, Death, Sudden, Cardiac, Potassium Channels, Voltage-Gated, KCNQ1 Potassium Channel, Mutation, Humans, Female, cardiovascular diseases, Polymorphism, Single-Stranded Conformational
Abstract

Long QT syndrome (LQTS) is the prototype of the cardiac ion channelopathies which cause syncope and sudden death. LQT1, due to mutations of KCNQ1 (KVLQT1), is the most common form. This study describes the genotype-phenotype characteristics in 10 families with mutations of KCNQ1, including 5 novel mutations. One hundred and two families with a history of lethal cardiac events, 55 LQTS, 9 Brugada syndrome, 18 idiopathic ventricular fibrillation (IVF), and 20 acquired LQTS, were studied by single-strand conformational polymorphism (SSCP) and DNA sequence analyzes. Families found to have KCNQ1 mutations were phenotyped using ECG parameters and cardiac event history, and genotype-phenotype correlation was performed. No mutations were found in Brugada syndrome, IVF, or acquired LQTS families. Ten out of 55 LQTS families had KCNQ1 mutations and 62 carriers were identified. Mutations included G269S in domain S5; W305X, G314C, Y315C, and D317N in the pore region; A341E and Q357R in domain S6; and 1338insC, G568A and T587M mutations in the C-terminus. W305X, G314C, Q357R, 1338insC, and G568A, appeared to be novel mutations. Gene carriers were 26 +/- 19 years (32 females). Baseline QTc was 0.47 +/- 0.03 s (range 0.40-0.57 s) and 40% had normal to borderline QTc (or = 0.46 s). Typical LQT1 T wave patterns were present in at least one affected member of each family, and in 73% of all affected members. A history of cardiac events was present in 19/62 (31%), 18 with syncope, 2 with aborted cardiac arrest (ACA) and six with sudden death (SD). Two out of 6 SDs (33%) occurred as the first symptom. No difference in phenotype was evident in pore vs. non-pore mutations. KCNQ1 mutations were limited to LQTS families. All five novel mutations produced a typical LQT1 phenotype. Findings emphasize (1) reduced penetrance of QTc and symptoms, resulting in diagnostic challenges, (2) the problem of sudden death as the first symptom (33% of those who died), and (3) genetic testing is important for identification of gene carriers with reduced penetrance, in order to provide treatment and to prevent lethal cardiac arrhythmias and sudden death.

Published
2003

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