Smits Jeroen P P, Eckardt Lars, Probst Vincent, Bezzina Connie R, Schott Jean Jacques, Remme Carol Ann, Haverkamp Wilhelm, Breithardt Günter, Escande Denis, Schulze-Bahr Eric, LeMarec Hervé, Wilde Arthur A M
Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
J Am Coll Cardiol. 2002 Jul 17;40(2):350-6. doi: 10.1016/s0735-1097(02)01962-9.
We have tested whether a genotype-phenotype relationship exists in Brugada syndrome (BS) by trying to distinguish BS patients with (carriers) and those without (non-carriers) a mutation in the gene encoding the cardiac sodium channel (SCN5A) using clinical parameters.
Brugada syndrome is an inherited cardiac disease characterized by a varying degree of ST-segment elevation in the right precordial leads and (non)specific conduction disorders. In a minority of patients, SCN5A mutations can be found. Genetic heterogeneity has been demonstrated, but other causally related genes await identification. If a genotype-phenotype relationship exists, this might facilitate screening.
In a multi-center study, we have collected data on demographics, clinical history, family history, electrocardiogram (ECG) parameters, His to ventricle interval (HV), and ECG parameters after pharmacologic challenge with I(Na) blocking drugs for BS patients with (n = 23), or those without (n = 54), an identified SCN5A mutation.
No differences were found in demographics, clinical history, or family history. Carriers had a significantly longer PQ interval on the baseline ECG and a significantly longer HV time. A PQ interval of > or =210 ms and an HV interval > or =60 ms seem to be predictive for the presence of an SCN5A mutation. After I(Na) blocking drugs, carriers had significantly longer PQ and QRS intervals and more increase in QRS duration.
We observed significantly longer conduction intervals on baseline ECG in patients with established SCN5A mutations (PQ and HV interval and, upon class I drugs, more QRS increase). These results concur with the observed loss of function of mutated BS-related sodium channels. Brugada syndrome patients with, and those without, an SCN5A mutation can be differentiated by phenotypical differences.
我们通过尝试使用临床参数区分编码心脏钠通道（SCN5A）基因存在突变的Brugada综合征（BS）患者（携带者）和不存在该突变的患者（非携带者），来检验BS中是否存在基因型-表型关系。
Brugada综合征是一种遗传性心脏病，其特征为右胸前导联ST段抬高程度不同以及（非）特异性传导障碍。在少数患者中可发现SCN5A突变。已证实存在遗传异质性，但其他因果相关基因有待确定。如果存在基因型-表型关系，这可能有助于筛查。
在一项多中心研究中，我们收集了有关人口统计学、临床病史、家族史、心电图（ECG）参数、希氏束至心室间期（HV）以及对已确定存在（n = 23）或不存在（n = 54）SCN5A突变的BS患者使用I（Na）阻断药物进行药物激发后的ECG参数的数据。
在人口统计学、临床病史或家族史上未发现差异。携带者在基线ECG上的PQ间期明显更长，HV时间明显更长。PQ间期≥210毫秒和HV间期≥60毫秒似乎可预测SCN5A突变的存在。使用I（Na）阻断药物后，携带者的PQ和QRS间期明显更长，QRS时限增加更多。
我们观察到已确定存在SCN5A突变的患者在基线ECG上的传导间期明显更长（PQ和HV间期，以及使用I类药物后QRS增加更多）。这些结果与观察到的与BS相关的突变钠通道功能丧失一致。存在和不存在SCN5A突变的Brugada综合征患者可通过表型差异进行区分。
