Pathogenicity of Hypertrophic Cardiomyopathy Variants: A Path Forward Together.
Pathogenicity of Hypertrophic Cardiomyopathy Variants: A Path Forward Together.
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肥厚型心肌病变异体的致病性：共同前进的道路。
DOI：
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发表时间：
2017
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影响因子：
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通讯作者：
B. Funke
中科院分区：
文献类型：
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作者：
J. Ingles;C. Burns;B. Funke
正确解释通过肥厚型心肌病（HCM）患者基因检测发现的罕见变异的挑战是普遍存在的。HCM基因检测已经提供了近20年，尽管我们的理解有了飞跃，但这种疾病的遗传基础在许多患者中仍然难以捉摸。随着技术的发展，综合心脏基因组的主流应用变得越来越便宜，检测到40%至60%的患者中具有临床意义的变异，其中大多数变异存在于编码心脏肌节的基因中。1，2在先证者中识别致病变异的价值延伸到家庭成员，他们可以选择最终知道自己是否携带致病变异，从而可以进行更有针对性的临床监测，并明确儿童面临的风险。然而，对于许多其他人来说，识别不确定的变异带来了更大的挑战，目前将其分类为致病性或良性的专业知识，资源和标准化标准都不足。
参见Furqan et al的文章
在本期《循环》中：心血管遗传学，Furqan等人3证明了在世界各地的专业HCM中心之间观察到的显著不一致性。在肌节性人类心肌病登记中心中，在>1个中心中观察到的20.5%的变体具有影响临床管理的分类差异，即可能的致病性/致病性或不确定意义的变体或可能的良性/良性。在75%的病例中，主要原因是通过肌节性人类心肌病登记中心（60%）或基因检测实验室的内部经验（60%）访问私人持有的数据。分离信息来自信息的家庭占35%的不一致的变异，...
The challenges of correctly interpreting rare variants identified via genetic testing of patients with hypertrophic cardiomyopathy (HCM) are universal and ever present. HCM genetic testing has been offered for almost 2 decades, yet in spite of the leaps forward in our understanding, the genetic underpinnings of this disease remain elusive in many patients. Mainstream application of comprehensive cardiac gene panels, which are becoming more affordable as the technology develops, detect a clinically significant variant in 40% to 60% of patients with the majority of variants residing in genes encoding the cardiac sarcomere.1,2 The value of identifying a pathogenic variant in a proband extends to family members, who have the option to know conclusively whether they carry the causative variant, allowing more targeted clinical surveillance and clarifying risk to children. For many others, however, the identification of uncertain variants poses greater challenges, and the expertise, resources, and standardized criteria to classify them as causative or benign currently fall short.
See Article by Furqan et al
In this issue of Circulation: Cardiovascular Genetics , Furqan et al3 demonstrate the marked discordance seen between specialist HCM centers worldwide. Among sarcomeric human cardiomyopathy registry centers, 20.5% of variants seen in >1 center had classification discrepancies that impacted clinical management, that is, likely pathogenic/pathogenic or variant of uncertain significance or likely benign/benign. The primary reason, in 75% of cases, was access to privately held data by either the sarcomeric human cardiomyopathy registry center (60%) or from the genetic testing laboratory’s internal experience (60%). Segregation information from informative families accounted for 35% of discordant variants, …