Seiko Ohno1, Masato Omura2, Mihoko Kawamura1, Hiromi Kimura1, Hideki Itoh1, Takeru Makiyama3, Hiroya Ushinohama4, Naomasa Makita5, Minoru Horie6. 1. Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan. 2. Cardiovasacular Department, Saiseikai Shimonoseki General Hospital, Shimonoseki 759-6603, Japan. 3. Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. 4. Cardiovascular Department, Fukuoka Children's Hospital and Medical Center for infectious disease, Fukuoka 810-0063, Japan. 5. Department of Molecular Physiology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8523, Japan. 6. Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan horie@belle.shiga-med.ac.jp.
Abstract
AIMS: Ryanodine receptor gene (RYR2) mutations are well known to cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Recently, RYR2 exon 3 deletion has been identified in patients with dilated cardiomyopathy (DCM) and/or CPVT. This study aimed to screen for the RYR2 exon 3 deletion in CPVT probands, characterize its clinical pathology, and confirm the genomic rearrangement. METHODS AND RESULTS: Our cohort consisted of 24 CPVT probands. Polymerase chain reaction (PCR)-based conventional genetic analysis did not identify any mutations in coding exons of RYR2 in these probands. They were screened using multiplex ligation-dependent probe amplification (MLPA). In probands identified with RYR2 exon 3 deletion, the precise location of the deletion was identified by quantitative PCR and direct sequencing methods. We identified two CPVT probands from unrelated families who harboured a large deletion including exon 3. The probands were 9- and 17-year-old girls. Both probands had a history of syncope related to emotional stress or exercise, exhibited bradycardia, and were diagnosed with left ventricular non-compaction (LVNC). We examined 10 family members and identified six more RYR2 exon 3 deletion carriers. In total, there were eight carriers, of which seven were diagnosed with LVNC (87.5%). Two carriers under the age of 4 years remained asymptomatic, although they were diagnosed with LVNC. Using quantitative PCR and direct sequencing, we confirmed that the deletions were 1.1 and 37.7 kb in length. CONCLUSION: RYR2 exon 3 deletion is frequently associated with LVNC. Therefore, detection of the deletion offers a new modality for predicting the prognosis of patients with LVNC with ventricular/atrial arrhythmias, particularly in children. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Ryanodine receptor gene (RYR2) mutations are well known to cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Recently, RYR2 exon 3 deletion has been identified in patients with dilated cardiomyopathy (DCM) and/or CPVT. This study aimed to screen for the RYR2 exon 3 deletion in CPVT probands, characterize its clinical pathology, and confirm the genomic rearrangement. METHODS AND RESULTS: Our cohort consisted of 24 CPVT probands. Polymerase chain reaction (PCR)-based conventional genetic analysis did not identify any mutations in coding exons of RYR2 in these probands. They were screened using multiplex ligation-dependent probe amplification (MLPA). In probands identified with RYR2 exon 3 deletion, the precise location of the deletion was identified by quantitative PCR and direct sequencing methods. We identified two CPVT probands from unrelated families who harboured a large deletion including exon 3. The probands were 9- and 17-year-old girls. Both probands had a history of syncope related to emotional stress or exercise, exhibited bradycardia, and were diagnosed with left ventricular non-compaction (LVNC). We examined 10 family members and identified six more RYR2 exon 3 deletion carriers. In total, there were eight carriers, of which seven were diagnosed with LVNC (87.5%). Two carriers under the age of 4 years remained asymptomatic, although they were diagnosed with LVNC. Using quantitative PCR and direct sequencing, we confirmed that the deletions were 1.1 and 37.7 kb in length. CONCLUSION:RYR2 exon 3 deletion is frequently associated with LVNC. Therefore, detection of the deletion offers a new modality for predicting the prognosis of patients with LVNC with ventricular/atrial arrhythmias, particularly in children. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Lisa M Wren; Juan Jiménez-Jáimez; Saleh Al-Ghamdi; Jumana Y Al-Aama; Amnah Bdeir; Zuhair N Al-Hassnan; Jyn L Kuan; Roger Y Foo; Franck Potet; Christopher N Johnson; Miriam C Aziz; Gemma L Carvill; Juan-Pablo Kaski; Lia Crotti; Francesca Perin; Lorenzo Monserrat; Paul W Burridge; Peter J Schwartz; Walter J Chazin; Zahurul A Bhuiyan; Alfred L George Journal: Circ Genom Precis Med Date: 2019-08-27
Authors: Andrés R Pérez-Riera; Raimundo Barbosa-Barros; Marianne P C de Rezende Barbosa; Rodrigo Daminello-Raimundo; Augusto A de Lucca; Luiz C de Abreu Journal: Ann Noninvasive Electrocardiol Date: 2017-10-19 Impact factor: 1.468