Department of Radiology, University of Utah, Salt Lake City, UT, USA.
Department of Pathology, University of Utah, Salt Lake City, UT, USA.
Genet Med. 2020 Jul;22(7):1201-1205. doi: 10.1038/s41436-020-0775-8. Epub 2020 Apr 17.
Determine the variant detection rate for ENG, ACVRL1, and SMAD4 in individuals who meet consensus (Curaçao) criteria for the clinical diagnosis of hereditary hemorrhagic telangiectasia.
Review of HHT center database for individuals with three or more HHT diagnostic criteria, in whom molecular genetic analysis for ENG, ACVRL1, and SMAD4 had been performed.
A variant known or suspected to be causal was detected in ENG in 67/152 (44.1%; 95% confidence interval [CI], 36.0-52.4%), ACVRL1 in 79/152 (52.0%; 95% CI, 43.7-60.1%), and SMAD4 in 2/152 (1.3%; 95% CI, 0.2-4.7%) family probands with definite HHT. Only 4/152 (2.6%; 95% CI, 0.7-6.6%) family probands did not have a variant in one of these genes.
Previous reports of the variant detection rate for ENG and ACVRL1 in HHT patients have come from laboratories, which receive samples from clinicians with a wide range of expertise in recognizing clinical manifestations of HHT. These studies suggest a significantly lower detection rate (~75-85%) than we have found in patients who meet strictly applied consensus criteria (96.1%). Analysis of SMAD4 adds an additional detection rate of 1.3%. HHT as defined by the Curaçao criteria is highly predictive of a causative variant in either ENG or ACVRL1.
确定符合遗传性出血性毛细血管扩张症临床诊断共识（Curaçao）标准的个体中 ENG、ACVRL1 和 SMAD4 的变异检出率。
回顾 HHT 中心数据库中符合三个或更多 HHT 诊断标准的个体，对其进行 ENG、ACVRL1 和 SMAD4 的分子遗传学分析。
在 152 名明确诊断为 HHT 的家系先证者中，ENG 中检测到已知或疑似致病的变异 67 例（44.1%；95%置信区间[CI]，36.0-52.4%），ACVRL1 中检测到 79 例（52.0%；95%CI，43.7-60.1%），SMAD4 中检测到 2 例（1.3%；95%CI，0.2-4.7%）。只有 4/152（2.6%；95%CI，0.7-6.6%）名家系先证者未在这些基因中的任何一个中发现变异。
先前 ENG 和 ACVRL1 在 HHT 患者中的变异检出率报告来自于接收具有广泛识别 HHT 临床表现专业知识的临床医生样本的实验室。这些研究表明，与我们在严格应用共识标准（96.1%）的患者中发现的变异检出率（~75-85%）相比，检出率显著降低。对 SMAD4 的分析增加了 1.3%的检出率。根据 Curaçao 标准定义的 HHT 高度预测 ENG 或 ACVRL1 中存在致病变异。
