Dataset Information

Mutational spectrum of the NKX2-5 gene in patients with lone atrial fibrillation.

ABSTRACT: Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia in humans and is responsible for substantial morbidity and mortality worldwide. Emerging evidence indicates that abnormal cardiovascular development is involved in the pathogenesis of AF. In this study, the coding exons and splice sites of the NKX2-5 gene, which encodes a homeodomain-containing transcription factor essential for cardiovascular genesis, were sequenced in 146 unrelated patients with lone AF as well as the available relatives of the mutation carriers. A total of 700 unrelated ethnically matched healthy individuals used as controls were genotyped. The disease-causing potential of the identified NKX2-5 variations was predicted by MutationTaster and PolyPhen-2. The functional characteristics of the mutant NKX2-5 proteins were analyzed using a dual-luciferase reporter assay system. As a result, two heterozygous NKX2-5 mutations, including a previously reported p.E21Q and a novel p.T180A mutation, were identified in two families with AF transmitted in an autosomal dominant pattern. The mutations co-segregated with AF in the families with complete penetrance. The detected substitutions, which altered the amino acids highly conserved evolutionarily across species, were absent in 700 control individuals and were both predicted to be causative. Functional analyses demonstrated that the NKX2-5 mutants were associated with significantly decreased transcriptional activity compared with their wild-type counterpart. The findings expand the spectrum of NKX2-5 mutations linked to AF and provide additional evidence that dysfunctional NKX2-5 may confer vulnerability to AF, suggesting the potential benefit for the early prophylaxis and personalized treatment of AF.

SUBMITTER: Yu H

PROVIDER: S-EPMC4003540 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Mutational spectrum of the NKX2-5 gene in patients with lone atrial fibrillation.

Yu Hong H Xu Jia-Hong JH Song Hao-Ming HM Zhao Lan L Xu Wen-Jun WJ Wang Juan J Li Ruo-Gu RG Xu Lei L Jiang Wei-Feng WF Qiu Xing-Biao XB Jiang Jin-Qi JQ Qu Xin-Kai XK Liu Xu X Fang Wei-Yi WY Jiang Jin-Fa JF Yang Yi-Qing YQ

International journal of medical sciences 20140407 6

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia in humans and is responsible for substantial morbidity and mortality worldwide. Emerging evidence indicates that abnormal cardiovascular development is involved in the pathogenesis of AF. In this study, the coding exons and splice sites of the NKX2-5 gene, which encodes a homeodomain-containing transcription factor essential for cardiovascular genesis, were sequenced in 146 unrelated patients with lone AF as well as ...[more]

PMID: 24782644

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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

Mutational spectrum of the NKX2-5 gene in patients with lone atrial fibrillation.

Publications

Mutational spectrum of the NKX2-5 gene in patients with lone atrial fibrillation.

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