A novel 5′ splice site mutation of SCN5A associated with Brugada syndrome resulting in multiple cryptic transcripts

Shimada, Toshio; Ohkubo, Kimie; Abé, Keisuke; Watanabe, Ichiro; Makita, Naomasa

doi:10.1016/j.ijcard.2012.04.114

Cited by 2 publications

(1 citation statement)

References 8 publications

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“…A minigene with this mutation produced multiple mature transcripts with exclusion of the last 100 bp of exon 25, exclusion of the first four bp of exon 26, or intron 25 retention. 49 Abnormal splicing of SCN5A without mutations has also been reported in patients with myotonic dystrophy type 1 (DM1) with BrS. 50 DM1 is the most common inherited neuromuscular disease in adults and is caused by an expansion of a (CTG)n triplet repeat in the 3′ region of the gene encoding dystrophia myotonica protein kinase.…”

Section: Mrna Processingmentioning

confidence: 99%

Ion channel messenger RNA processing defects and arrhythmia

Zhou¹,

Dudley²

2014

CBF

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Messenger RNA (mRNA) processing is an essential step for the expression of most eukaryote genes. Ion channels are critical for proper electrical activity in the heart, and perturbations of these channels are known to cause arrhythmia. Recently, mRNA processing defects have been shown to contribute to altered ion channel activity and arrhythmogenesis. Abnormal pre-mRNA splicing of cardiac ion channels, including the cardiac sodium channel, potassium channels, and calcium channels, because of mutations of the cis-elements within the RNA or abnormal expression of splicing factors, has been documented to contribute to arrhythmic risk. In addition to pre-mRNA splicing, other mRNA processing events, such as 3′-end formation and mRNA turnover, are also disrupted in cardiac diseases, such as congenital heart disease caused by mutation at the 3′-untranslated region of GATA4. mRNA stability is also dysregulated by altered expression of microRNAs in atrial fibrillation. In this review, we discuss our current understanding of how mRNA processing defects contribute to the risk of arrhythmias and how monitoring the products of abnormal processing may lead to diagnostic tests for arrhythmic risk.

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Section: Mrna Processingmentioning

confidence: 99%

Ion channel messenger RNA processing defects and arrhythmia

Zhou¹,

Dudley²

2014

CBF

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Cardiac Emerinopathy

Ishikawa

Mishima

Barc

et al. 2020

Circ: Arrhythmia and Electrophysiology

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Background: Mutations in the nuclear envelope genes encoding LMNA and EMD are responsible for Emery-Dreifuss muscular dystrophy. However, LMNA mutations often manifest dilated cardiomyopathy with conduction disturbance without obvious skeletal myopathic complications. On the contrary, the phenotypic spectrums of EMD mutations are less clear. Our aims were to determine the prevalence of nonsyndromic forms of emerinopathy, which may underlie genetically undefined isolated cardiac conduction disturbance, and the etiology of thromboembolic complications associated with EMD mutations. Methods: Targeted exon sequencing was performed in 87 probands with familial sick sinus syndrome (n=36) and a progressive cardiac conduction defect (n=51). Results: We identified 3 X-linked recessive EMD mutations (start-loss, splicing, missense) in families with cardiac conduction disease. All 3 probands shared a common clinical phenotype of progressive atrial arrhythmias that ultimately resulted in atrial standstill associated with left ventricular noncompaction (LVNC), but they lacked early contractures and progressive muscle wasting and weakness characteristic of Emery-Dreifuss muscular dystrophy. Because the association of LVNC with EMD has never been reported, we further genetically screened 102 LVNC patients and found a frameshift EMD mutation in a boy with progressive atrial standstill and LVNC without complications of muscular dystrophy. All 6 male EMD mutation carriers of 4 families underwent pacemaker or defibrillator implantation, whereas 2 female carriers were asymptomatic. Notably, a strong family history of stroke observed in these families was probably due to the increased risk of thromboembolism attributable to both atrial standstill and LVNC. Conclusions: Cardiac emerinopathy is a novel nonsyndromic X-linked progressive atrial standstill associated with LVNC and increased risk of thromboembolism.

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A novel 5′ splice site mutation of SCN5A associated with Brugada syndrome resulting in multiple cryptic transcripts

Cited by 2 publications

References 8 publications

Ion channel messenger RNA processing defects and arrhythmia

Ion channel messenger RNA processing defects and arrhythmia

Cardiac Emerinopathy

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