[SCD-FORUM] 51E RE:无症状性Brugada综合征病人――Li Zhang医师

[SCD Symposium]

51E RE:无症状性Brugada综合征病人――Li Zhang医师
尊敬的Ray医生：
首先，非常感谢你为论坛提供了这么好的一个问题， 
我希望专家组的Igor Splawski, Silvia  Priori, 和 Michael  
Ackerman博士能给你一个满意的答复。因所知有限，对 
于您的问题，我的或许是不成熟的看法是不能排除。 
即便是标准基因检测方法得到的阴性结果，也不能排 
除体细胞突变致病的可能。两年前，Splawski博士等人 
在绝大多数Timothy综合征(LQT8)的散发病例中发现了与 
致病相关的Cav1.2 钙通道基因上G406R的突变。研究发 
现，患病者中有两个孩子是同胞，而且从他们父母的 
血样中抽提的DNA并未发现突变。但是lgor在母亲的颊 
拭子DNA样本（来源于口腔粘膜）中发现了突变。这一 
发现提示她是一个嵌和子。这意味着在她早期发育阶 
段，G406R开始形成。(Splawski, et al Cell, 2004;119:1-20).
昨晚我怀着极大的兴趣阅读了Calum MacRae博士写的与 
Garcia-Gras博士等人所做精彩研究（J. Clin. Invest  
2006;116:2012-21，题目为suppression of canonical Wnt/beta- catenin  
signaling by nuclear plakoglobin recapitulates phenotype of   
arrhythmogenic right ventricular cardiomyopathy.）有关的评论 
（MacRae, et al J. Clin. 2006, Invest;116:1825-28）。我希望这 
些信息能对你有所帮助。
致

Li Zhang 博士

――－
Sergio Dubner博士
科委会主席
  Edgardo Schapachnik博士
组委会主席
张欣译 王玲洁校


51E RE: Asymptomatic patient with Brugada syndrome. Dr. Li Zhang
Dear Dr. Ray:
    Thank you so much for contributing such an excellent question to
www.scd-symposium.org. I wish experts Drs. Igor Splawski, Silvia
Priori, and Michael Ackerman would be able to provide you the answer
in satisfactory.
    With very limited knowledge, my premature response to your
question is no. A negative genetic testing result by a standard
approach cannot ruled out the possibility of somatic mutation caused
diseases. Two years ago, Dr. Splawski, et al identified the disease-
causing mutation G406R in Cav1.2 calcium channel gene in most of
sporadic cases with Timothy syndrome (LQT8). Two of affected children
are siblings, and the DNA extracted from the parents' blood sample do
not have the mutation. However, Igor found the mutation in their
mother's buccal swab DNA sample (from oral mucosa), suggesting she is
a mosaic. It means G406R arose de novo during her early development.
(Splawski, et al Cell, 2004;119:1-20).
    Last night I had a great interest reading Dr. Calum MacRae's
commentaries (MacRae, et al J. Clin. 2006, Invest;116:1825-28)
regarding an excellent study conducted by Dr. Garcia-Gras, et al. J.
Clin. Invest 2006;116:2012-21 (suppression of canonical Wnt/beta-
catenin signaling by nuclear plakoglobin recapitulates phenotype of
arrhythmogenic right ventricular cardiomyopathy. I wish those
information could be helpful to you as well.

Sincerely,

Li Zhang, MD

--
Dr. Sergio Dubner
President of Scientific Committee

Dr. Edgardo Schapachnik
President of Steering Committee

>
> 44E RE: 无症状性Brugada综合征病人――Ray Jordan 医师
> 尊敬的李医师：
> 首先，是否已通过基因研究分析排除了可用来解释离
> 子通道病变表型多样性或临床表现多样性的等位基因
> 嵌和现象（发生在器官形成和胚胎分化阶段）。还有
> 需要说明的一点是，一些等位基因更易在第八脑神
> 经、左室、右室等部位出现，而其他部位的起搏细胞
> 可完全正常。
>
> Richar-Ray/dba Richard Ray Jordan, M.D., SFM
> ――
> Sergio Dubner 博士
> 科委会主席
> Edgardo Schapachnik 博士
> 组委会主席
>
>   44E RE: Asymptomatic patient with Brugada syndrome. Dr. Ray Jordan
> Dr. Li,
> Has genetic research analysis ruled out genetic allele chimerism  
> (at the
> time of organogenesis and embryological differentiation) to explain  
> the
> phenotypic variety of channelopathies or numerous clinical
> manifestations? Another words are some alleles more likely to find or
> gravitate towards the  eighth nerve, RV, vs LV etc., while other
> regions of pacemaker cells remain  entirely normal?
> Richar-Ray/dba Richard Ray Jordan, M.D., SFM