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Updated: Jul 19, 2026
Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
Postmortem molecular screening for cardiac ryanodine receptor type 2 mutations in sudden unexplained death: R420W
Hajime Nishio1, Misa Iwata, Koichi Suzuki
1Department of Legal Medicine, Osaka Medical College, Takatsuki 569-8686, Japan. leg010@art.osaka-med.ac.jp
Background:
Mutations of the cardiac ryanodine receptor type 2 (RyR2) gene are known to cause effort-induced polymorphic ventricular arrhythmia, syncope and sudden death.
Methods And Results:
The possible mutations in the RyR2 gene were examined in 18 autopsy cases of sudden unexplained death (SUD). Two cases were found to have the heterozygous missense mutation in exon 14 (nucleotide change C1258T, coding effect R420W). Both cases showed mild fatty infiltration of the right ventricular apex. Interestingly, 1 case showed an enlarged thymus with accompanying hypertrophy of the tonsils and mesenteric lymph nodes. In addition, a narrowing of the aorta was observed in this case. These phenotypic characteristics are consistent with status thymico-lymphaticus, which combines sudden death with an enlargement of lymphoid organs and hypoplasia of the cardiovascular system. The second case also displayed some characteristics of status thymico-lymphaticus.
Conclusion:
The R420W mutation has already been reported in families with juvenile sudden death and may be causative of sudden death in our cases. Postmortem molecular screening of the RyR2 gene could be useful for investigation for cause of death in SUD. The possible association of the RyR2 mutation with status thymico-lymphaticus is discussed.
Insights
Cardiac ryanodine receptor type 2 (RyR2) gene mutations, specifically R420W, may cause sudden unexplained death (SUD). This RyR2 mutation was found in two autopsy cases, one with characteristics of status thymico-lymphaticus.
Area of Science:
- Cardiovascular Genetics
- Forensic Pathology
- Molecular Biology
Background:
- Mutations in the cardiac ryanodine receptor type 2 (RyR2) gene are linked to sudden cardiac death.
- Effort-induced polymorphic ventricular arrhythmias, syncope, and sudden death are known consequences.
Purpose of the Study:
- To investigate RyR2 gene mutations in autopsy cases of sudden unexplained death (SUD).
- To explore potential links between RyR2 mutations and specific pathological findings.
Main Methods:
- Screening of the RyR2 gene in 18 autopsy cases of SUD.
- Analysis of genetic mutations and postmortem phenotypic characteristics.
Main Results:
- Two cases (11%) revealed a heterozygous missense mutation (R420W) in exon 14 of the RyR2 gene.
- Both mutation-positive cases exhibited mild fatty infiltration of the right ventricular apex.
- One case presented with features consistent with status thymico-lymphaticus, including thymic enlargement and aortic narrowing; the second case showed some similar characteristics.
Conclusions:
- The identified R420W RyR2 mutation, previously associated with juvenile sudden death, may be causative in these SUD cases.
- Postmortem molecular screening of the RyR2 gene is a valuable tool for SUD investigations.
- A potential association between RyR2 mutations and status thymico-lymphaticus warrants further discussion and research.
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