TY - JOUR
T1 - Postmortem genetic testing of the ryanodine receptor 2 (RYR2) gene in a cohort of sudden unexplained death cases
AU - Larsen, M. K.
AU - Berge, K. E.
AU - Leren, T. P.
AU - Nissen, P. H.
AU - Hansen, J.
AU - Kristensen, I. B.
AU - Banner, J.
AU - Jensen, H. K.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - The aim of this investigation was to identify pathogenic variants of the ryanodine receptor 2 (RYR2) gene in a cohort of persons aged 0-40 years who died of sudden unexpected death syndrome (SUD), including a cohort of infants who died of sudden infant death syndrome (SIDS). We genetically screened 29 of the 105 exons of the RYR2 gene associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) in 74 cases of SUD without reported structural abnormalities of the heart. Cases were selected from the case database at the Institute of Forensic Medicine, and subsequent mutational screening by DNA sequencing was performed to detect variants in DNA samples extracted from blood samples of deceased persons. A total of 7 of the examined 74 cases were heterozygous for a rare sequence variant in the RYR2 gene. We identified five novel missense variants (p.Q486H, p.D1872N, p.G2367R, p.E4213D, and p.H4579Y), one synonymous variant (p.L4767L), and one previously reported missense variant (p.G4315E). Follow-up studies were possible in family members of three probands (p.Q486H, p.D1872N, and p.H4579Y), and clinical examinations were conducted in family members of two of these probands (p.Q486H and p.H4579Y). In conclusion, we identified a higher prevalence of variants in the CPVT-associated gene RYR2 than in a previously reported cohort of SIDS (9.4% vs. 1-2%). Segregation studies show that one variant (p.H4579Y) co-segregates with CPVT and is presumed to be pathogenic.
AB - The aim of this investigation was to identify pathogenic variants of the ryanodine receptor 2 (RYR2) gene in a cohort of persons aged 0-40 years who died of sudden unexpected death syndrome (SUD), including a cohort of infants who died of sudden infant death syndrome (SIDS). We genetically screened 29 of the 105 exons of the RYR2 gene associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) in 74 cases of SUD without reported structural abnormalities of the heart. Cases were selected from the case database at the Institute of Forensic Medicine, and subsequent mutational screening by DNA sequencing was performed to detect variants in DNA samples extracted from blood samples of deceased persons. A total of 7 of the examined 74 cases were heterozygous for a rare sequence variant in the RYR2 gene. We identified five novel missense variants (p.Q486H, p.D1872N, p.G2367R, p.E4213D, and p.H4579Y), one synonymous variant (p.L4767L), and one previously reported missense variant (p.G4315E). Follow-up studies were possible in family members of three probands (p.Q486H, p.D1872N, and p.H4579Y), and clinical examinations were conducted in family members of two of these probands (p.Q486H and p.H4579Y). In conclusion, we identified a higher prevalence of variants in the CPVT-associated gene RYR2 than in a previously reported cohort of SIDS (9.4% vs. 1-2%). Segregation studies show that one variant (p.H4579Y) co-segregates with CPVT and is presumed to be pathogenic.
KW - Catecholaminergic polymorphic ventricular tachycardia
KW - Forensic pathology
KW - Forensic sciences
KW - RYR2 gene
KW - Sudden unexpected death
U2 - 10.1007/s00414-011-0658-2
DO - 10.1007/s00414-011-0658-2
M3 - Journal article
C2 - 22222782
AN - SCOPUS:84872401976
SN - 0937-9827
VL - 127
SP - 139
EP - 144
JO - International Journal of Legal Medicine
JF - International Journal of Legal Medicine
IS - 1
ER -