Creighton Wendy, Virmani Renu, Kutys Robert, Burke Allen
Department of Pathology, University of Maryland School of Medicine, 685 W. Baltimore St., Room 7-34C, Baltimore, MD 21201-1192, USA.
J Mol Diagn. 2006 Feb;8(1):62-7. doi: 10.2353/jmoldx.2006.050081.
Mutations in the cardiac ryanodine type 2 receptor (RyR2) gene are associated with catecholaminergic polymorphic ventricular tachycardia. We hypothesized that these mutations could be detected at autopsy in cases of exercise-triggered sudden death. Fourteen sudden death patients, eight males and six females, were studied at autopsy based on apparent sudden cardiac death, without significant anatomical abnormalities. The coding regions of arrhythmia genes were amplified by polymerase chain reaction and directly sequenced. Three novel RyR2 mutations, R414C, F2331S, and R2401L, were identified in three unrelated patients (two males and one female; mean age at death, 12 +/- 2 years), all performing strenuous activity at the time of death or collapse. These mutations were located in highly conserved regions where arrhythmia-linked RyR2 mutations clustered. Although G269S in the KVLQT1 gene was detected in a female with known family history of syncope and sudden cardiac death, no other mutations were found in any of the 14 cases, and no other mutations was found in 200 controls. The absence of structural cardiac disease in physical activity-induced sudden death and the finding of three novel RyR2 mutations suggest that mutation screening in such cases should include RyR2.
心脏兰尼碱受体2型（RyR2）基因的突变与儿茶酚胺能多形性室性心动过速相关。我们推测，在运动诱发的猝死病例尸检中可检测到这些突变。对14例猝死患者（8例男性，6例女性）进行尸检研究，这些患者均为明显的心源性猝死，无明显解剖学异常。通过聚合酶链反应扩增心律失常相关基因的编码区并直接测序。在3例无亲缘关系的患者（2例男性和1例女性；平均死亡年龄12±2岁）中鉴定出3种新的RyR2突变，即R414C、F2331S和R2401L，所有患者在死亡或晕厥时均进行剧烈活动。这些突变位于心律失常相关的RyR2突变聚集的高度保守区域。尽管在1例有已知晕厥和心源性猝死家族史的女性中检测到KVLQT1基因的G269S突变，但在14例病例中未发现其他突变，在200例对照中也未发现其他突变。在体力活动诱发的猝死中未发现结构性心脏病，以及发现3种新的RyR2突变提示，在此类病例中进行突变筛查应包括RyR2。
