A family with a complex clinical presentation characterized by arrhythmogenic right ventricular dysplasia/cardiomyopathy and features of branchio-oculo-facial syndrome.
A family with a complex clinical presentation characterized by arrhythmogenic right ventricular dysplasia/cardiomyopathy and features of branchio-oculo-facial syndrome.
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该家族具有复杂的临床表现，以致心律失常性右心室发育不良/心肌病和鳃眼面部综合征为特征。
DOI：
10.1002/ajmg.a.35733
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Judge,DanielP
中科院分区：
文献类型：
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作者：
Murray,Brittney;Wagle,Rohan;Amat-Alarcon,Nuria;Wilkens,Alisha;Stephens,Paul;Zackai,ElaineH;Goldmuntz,Elizabeth;Calkins,Hugh;Deardorff,MatthewA;Judge,DanielP
致心律失常性右室发育不良/心肌病(ARVD/C)是一种家族性心肌病，通常由编码心脏桥粒成分的基因突变引起。BRANCHIO-OCULO-FACE综合征(BofS)是一种由TFAP2基因突变引起的头面部疾病。在一个分离ARVD/C的家庭中，一些成员也具有BofS的特征。对ARVD/C的基因检测发现了PKP2的突变，PKP2是心脏桥粒的一种成分，编码平台亲和素-2。染色体微阵列检测发现染色体6p24处有4.4Mb缺失，包括TFAP2A和编码桥粒蛋白的DSP，这是与ARVD/C相关的心脏桥粒的一个附加成分。同时存在6p24缺失和PKP_2突变的家族成员有更严重的心功能障碍。这些发现表明，这种连续的基因缺失同时导致ARVD/C和BofS，而DSP单倍体不足可能导致心肌病。这个家族提供了一个临床例子，强调了在已知存在遗传异质性的临床方案中进行仔细评估的必要性。最后，它表明，患有不明原因心肌病和面部特征变形的个人可能从CMA分析中受益。©2013 Wiley期刊，Inc.
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a familial form of cardiomyopathy typically caused by mutations in genes that encode an element of the cardiac desmosome. Branchio‐oculo‐facial syndrome (BOFS) is a craniofacial disorder caused byTFAP2Amutations. In a family segregating ARVD/C, some members also had features of BOFS. Genetic testing for ARVD/C identified a mutation inPKP2, encoding plakophilin‐2, a component of the cardiac desmosome. Evaluation of dysmorphology by chromosome microarray (CMA) identified a 4.4 Mb deletion at chromosome 6p24 that included bothTFAP2AandDSP, encoding desmoplakin, an additional component of the cardiac desmosome implicated in ARVD/C. A family member with both the 6p24 deletion andPKP2mutation had more severe cardiac dysfunction. These findings suggest that this contiguous gene deletion contributes to both ARVD/C and BOFS, and thatDSPhaploinsufficiency may contribute to cardiomyopathy. This family provides a clinical example that underscores the need for careful evaluation in clinical scenarios where genetic heterogeneity is known to exist. Finally, it suggests that individuals with unexplained cardiomyopathy and dysmorphic facial features may benefit from CMA analysis. © 2013 Wiley Periodicals, Inc.