临床遗传学-心血管遗传与基因组医学.pptVIP

* * Na+ current (LQT3, Brugada syndrome). Transient outward K+ current Rapid component of delayed rectifier K+ current (LQT2 + LQT6) Slow component of the delayed rectifier K+ current (LQT1 + LQT5) Ultra-rapid component of the delayed rectifier K+ current L-type Ca2+ current Inwardly rectifying K+ current (Andersen syndrome) Myocardial Transmembrane Action Potential INa: Ito: IKur: IKr: INa (IKur) Ito IKr IKs ICa(L) IKir IKs: ICa(L): IKir: What Triggers the Symptoms? Exercise Emotional excitements Sleep Drugs 临床方法 病史：要点 三代家族系谱，特别询问晕厥，“癫痫发作”，猝死和先天性耳聋的情况。 辅助检查 心电图，测量QTc。 收集DNA样本进行分子遗传学分析。 鉴别诊断 Jevell，Lange-Nielsen综合征是长QT间期综合征的纯合子形式，表现为明显的先天性耳聋和QT间期延长。常染色体隐性遗传，兄弟姐妹的再发风险是1/4。患者父母都是突变携带者，兄弟姐妹的携带风险是2/3。 Timothy综合征是一种罕见疾病，表现为长QT间期综合征和并指畸形，是由于L型钙离子通道CaV2.1的突变引起（Splawski）。其它表现包括轻度的面部畸形，先天性心脏病，间断性低血糖，认知功能异常和自闭症。 Brugada综合征是一种罕见的常染色体显性遗传疾病，~15%的患者是由于钠离子通道基因SCN5A（LQT3）的功能丧失突变引起，会出现各种心律失常，包括心动过缓，房室传导延迟和室颤（VF）。剩余85%患者的遗传基础目前未知。 肥厚性心肌病（HCM）患者易于发生威胁生命的心律失常。如果心律失常是引起猝死的原因，应进行尸检。 致心律失常性右心室发育不良（ARVD）或心肌病（ARVC） International LQTS Registry and LQTS Molecular Genetics Laboratory at Rochester International LQTS Registry - Established by Dr. Moss in 1979. - To date, 1206 proband-identified families have been enrolled. - Almost all important findings on LQTS directly came from or collaborated with this registry. LQTS Molecular Genetics Laboratory - Established in the Fall of 1999. - 800 samples are collected and mutational analysis is performed. - Many novel mutations have been identified. - Platform for genotype-phenotype co- relationship studies, identification of new LQT genes and modifier genes. LQTS Mutations by Type (from Splawski et al Circulation, 2000. 102:1178) LQTS Mutations by Positi