Identification of a Novel Homozygous Multi-Exon Duplication in RYR2 among Children with Exertion-Related Unexplained Sudden Deaths in the Amish Community

JAMA Cardiology

Volumn 5, Issue 3, 2020, Pages 340-345

  Tester, David J ^a,b   Bombei, Hannah M ^c   Fitzgerald, Kristi K ^d   Giudicessi, John R ^a,b   Pitel, Beth A ^b   Thorland, Erik C ^b   Russell, Barbara G ^e   Hamrick, Samantha K ^a,b   Kim, C S John ^a,b   Haglund Turnquist, Carla M ^a,b   Johnsrude, Christopher L ^e   Atkins, Dianne L ^c   Ochoa Nunez, Luis A ^c   Law, Ian ^c   Temple, Joel ^d   Ackerman, Michael J ^a,b  

^a MAYO GRADUATE SCHOOL   (United States)

^b MAYO CLINIC   (United States)

^c UNIVERSITY OF IOWA CHILDREN S HOSPITAL   (United States)

^d NEMOURS ALFRED I DUPONT HOSPITAL FOR CHILDREN   (United States)

^e University of Louisville School of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RYANODINE RECEPTOR 2; RYANODINE RECEPTOR;

5' UNTRANSLATED REGION; AMISH; ARTICLE; AUTOPSY; CHILD; CLINICAL ARTICLE; CONSANGUINITY; COPY NUMBER VARIATION; ECTOPIA CORDIS; EXERCISE; EXOME MOLECULAR AUTOPSY; EXON; FAINTNESS; FAMILY HISTORY; FEMALE; GENE DUPLICATION; GENETIC SCREENING; HEART RATE; HEART VENTRICLE EXTRASYSTOLE; HEART VENTRICLE FIBRILLATION; HOMOZYGOUS MULTI EXON DUPLICATION; HUMAN; MALE; MATE PAIR SEQUENCING; PRESCHOOL CHILD; PRIORITY JOURNAL; PROMOTER REGION; RECESSIVE INHERITANCE; RESUSCITATION; RYR2 GENE; SCHOOL CHILD; SUDDEN CARDIAC DEATH; SUDDEN DEATH; TORSADE DES POINTES; TREADMILL EXERCISE; ELECTROCARDIOGRAPHY; GENETICS; HEART VENTRICLE TACHYCARDIA; HOMOZYGOTE; PEDIGREE; SIBLING;

AMISH; CHILD; CHILD, PRESCHOOL; CONSANGUINITY; DEATH, SUDDEN, CARDIAC; DNA COPY NUMBER VARIATIONS; ELECTROCARDIOGRAPHY; EXONS; FEMALE; GENE DUPLICATION; GENETIC TESTING; HOMOZYGOTE; HUMANS; MALE; PEDIGREE; PHYSICAL EXERTION; PROMOTER REGIONS, GENETIC; RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL; SIBLINGS; TACHYCARDIA, VENTRICULAR;

EID: 85077978647     PISSN: 23806583     EISSN: 23806591     Source Type: Journal    
DOI: 10.1001/jamacardio.2019.5400     Document Type: Article

References (9)

1. Bagnall RD, Weintraub RG, Ingles J, A prospective study of sudden cardiac death among children and young adults. N Engl J Med. 2016; 374 (25): 2441-2452. doi: 10.1056/NEJMoa1510687 27332903
2. Ackerman MJ, Priori SG, Willems S, HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm. 2011; 8 (8): 1308-1339. doi: 10.1016/j.hrthm.2011.05.020 21787999
3. Strande NT, Riggs ER, Buchanan AH, Evaluating the clinical validity of gene-disease associations: An evidence-based framework developed by the Clinical Genome Resource. Am J Hum Genet. 2017; 100 (6): 895-906. doi: 10.1016/j.ajhg.2017.04.015 28552198
4. Bhuiyan ZA, van den Berg MP, van Tintelen JP, Expanding spectrum of human RYR2-related disease: New electrocardiographic, structural, and genetic features. Circulation. 2007; 116 (14): 1569-1576. doi: 10.1161/CIRCULATIONAHA.107.711606 17875969
5. Medeiros-Domingo A, Bhuiyan ZA, Tester DJ, The RYR2-encoded ryanodine receptor/calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long QT syndrome: A comprehensive open reading frame mutational analysis. J Am Coll Cardiol. 2009; 54 (22): 2065-2074. doi: 10.1016/j.jacc.2009.08.022 19926015
6. Marjamaa A, Laitinen-Forsblom P, Lahtinen AM, Search for cardiac calcium cycling gene mutations in familial ventricular arrhythmias resembling catecholaminergic polymorphic ventricular tachycardia. BMC Med Genet. 2009; 10 (1): 12. doi: 10.1186/1471-2350-10-12 19216760
7. Liu Y, Wang R, Sun B, Generation and characterization of a mouse model harboring the exon-3 deletion in the cardiac ryanodine receptor. PLoS One. 2014; 9 (4):
8. Ohno S, Omura M, Kawamura M, Exon 3 deletion of RYR2 encoding cardiac ryanodine receptor is associated with left ventricular non-compaction. Europace. 2014; 16 (11): 1646-1654. doi: 10.1093/europace/eut382 24394973
9. Takeshima H, Komazaki S, Hirose K, Nishi M, Noda T, Iino M. Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine receptor type 2. EMBO J. 1998; 17 (12): 3309-3316. doi: 10.1093/emboj/17.12.3309 9628868