Dataset Information

Prevalence and Spectrum of TBX5 Mutation in Patients with Lone Atrial Fibrillation.

ABSTRACT: Atrial fibrillation (AF), the most common type of cardiac rhythm disturbance encountered in clinical practice, is associated with substantially increased morbidity and mortality. Aggregating evidence demonstrates that abnormal cardiovascular development is involved in the pathogenesis of AF. A recent study has revealed that the TBX5 gene, which encodes a T-box transcription factor key to cardiovascular development, was associated with AF and atypical Holt-Oram syndrome. However, the prevalence and spectrum of TBX5 mutation in patients with lone AF remain unclear. In this study, the coding regions and splicing junction sites of TBX5 were sequenced in 192 unrelated patients with lone AF and 300 unrelated ethnically-matched healthy individuals used as controls. The causative potential of the identified TBX5 variation was evaluated by MutationTaster and PolyPhen-2. The functional effect of the mutant TBX5 was assayed by using a dual-luciferase reporter assay system. As a result, a novel heterozygous TBX5 mutation, p.H170D, was identified in a patient, with a mutational prevalence of approximately 0.52%. This mutation, which was absent in the 300 control individuals, altered the amino acid completely conserved evolutionarily across species, and was predicted to be disease-causing. Functional deciphers showed that the mutant TBX5 was associated with significantly reduced transcriptional activity when compared with its wild-type counterpart. Furthermore, the mutation significantly decreased the synergistic activation between TBX5 and NKX2-5 or GATA4. The findings expand the mutational spectrum of TBX5 linked to AF and provide new evidence that dysfunctional TBX5 may contribute to lone AF.

SUBMITTER: Wang ZC

PROVIDER: S-EPMC4747871 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Prevalence and Spectrum of TBX5 Mutation in Patients with Lone Atrial Fibrillation.

Wang Zhan-Cheng ZC Ji Wen-Hui WH Ruan Chang-Wu CW Liu Xing-Yuan XY Qiu Xing-Biao XB Yuan Fang F Li Ruo-Gu RG Xu Ying-Jia YJ Liu Xu X Huang Ru-Tai RT Xue Song S Yang Yi-Qing YQ

International journal of medical sciences 20160123 1

Atrial fibrillation (AF), the most common type of cardiac rhythm disturbance encountered in clinical practice, is associated with substantially increased morbidity and mortality. Aggregating evidence demonstrates that abnormal cardiovascular development is involved in the pathogenesis of AF. A recent study has revealed that the TBX5 gene, which encodes a T-box transcription factor key to cardiovascular development, was associated with AF and atypical Holt-Oram syndrome. However, the prevalence a ...[more]

PMID: 26917986

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Project description:RationaleAtrial fibrillation (AF) is encountered rarely in pregnancy. Management of maternal AF is challenging as it poses a threat to both maternal and fetal well-being.Patient concernsWe report a case of a 35 weeks pregnant woman who presented in emergency with sudden-onset palpitations and mild shortness of breath with no personal/family history of cardiac diseases.DiagnosesPatient's pulse was irregularly irregular with an average rate of 179 beats per minute. The obstetric examination was normal.DiagnosisHigh-sensitive cardiac troponin T (hs-cTnT) was elevated. The 12 lead electrocardiogram (ECG) confirmed AF. The obstetric ultrasound, electronic fetal heart rate (EFHR) trace, and maternal echocardiography were normal.InterventionsThe patient was admitted under joint cardiology and obstetric care and monitored with continuous telemetry. She was commenced on a therapeutic dose of low-molecular weight heparin (LMWH) and intravenous fluid. She received a single 200 Joule synchronized direct current (DC) shock under general anesthesia in operation theater, which reverted the rhythm back to normal. EFHR monitoring was normal pre- and post-DC cardioversion. We acknowledge the unwise use of therapeutic dose of LMWH before DC cardioversion (DCCV) because of a potential need for emergency cesarean delivery for maternal and/or fetal compromise.OutcomeThe patient remained well and in sinus rhythm after cardioversion. She was discharged home the following day on Flecainide (anti-arrhythmic) and therapeutic dose of low molecular weight heparin (LMWH) and followed up in outpatient clinics frequently. She had a baby at term and received prophylactic LMWH for 10 days post-cesarean. She was discharged from cardiology clinic when she was 10 weeks postnatal, and Flecainide was discontinued.LessonsWe are reporting this case because of the rarity of the condition and successful use of DCCV for treating maternal AF. High-sensitive cardiac troponin T (hs-cTnT) level is a useful laboratory indicator to gauge the severity of AF in pregnancy. We emphasize to make the arrangements for EFHR monitoring and potential cesarean delivery and advocate cautious use of thromboprophylaxis while planning for electrical cardioversion (ECV) for maternal AF.

Project description:Abstract Background Epicardial adipose tissue (EAT) has been considered as one of the probable triggers of atrial fibrillation (AF). CT‐rediomics is a perspective noninvasive method of assessment of EAT. We evaluate the radiomic phenotype of EAT in patients with lone AF in the prognosis of AF recurrence after catheter ablation. Methods A total of 43 patients with lone AF referred for CA and 20 out‐hospital patients without arrhythmia underwent multidetector computed tomography coronary angiography. Segmentation of EAT and extraction radiomic features were performed on calcium scoring series using by 3D‐Slicer. Clinical follow‐up was performed for 12 months period after the CA. Results EAT in patients with lone AF had a distinct radiomic phenotype. Thus, 45 of 93 calculated radiomic features, volume and attenuation of EAT were significantly different between patients with lone AF and persons without any arrhythmia. In addition, 17 radiomic features were significantly different in subgroups with and without AF recurrence. Multivariate regression analysis demonstrated that only gray level nonuniformity normalized (GLSZM) was an independent predictor of AF recurrence (OR 1.0027, 95%CI 1.0009–1.0044, p = 0.002). ROC analysis data showed that GLSZM >1227.4 indicates high probability of AF recurrence during 12 months (sensitivity 89.4%, specificity 70.8%, AUC: 0.809; p = 0.001). Conclusion The radiomic parameter GLSZM is associated with late AF recurrence after CA in patients with lone AF. In current study GLSZM was a stronger predictor of lone AF recurrence in multivariate analysis comparing with other established risk factors and EAT volume and attenuation. This study is a step forward towards the application of radiomic analisys for study the role of epicardial adipose tissue in the occurrence of AF recurrence after ablation. The results are significantly important due to the fact it was shown that the radiomic parameter GLSZM is associated with late AF recurrence after CA in patients without structural changes of myocardium. Moreover, GLSZM was the stronger predictor of isolated AF recurrence in multivariate analysis comparing with other established risk factors and EAT volume and attenuation.

Dataset Information

Prevalence and Spectrum of TBX5 Mutation in Patients with Lone Atrial Fibrillation.

Publications

Prevalence and Spectrum of TBX5 Mutation in Patients with Lone Atrial Fibrillation.

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