TBX5 变异与心脏表型:文献系统综述和一种新型变体。

IF 1.6 4区 医学 Q3 GENETICS & HEREDITY
Anne Kathrine Møller Nielsen , Anna Maria Dehn , Vibeke Hjortdal , Lars Allan Larsen
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引用次数: 0

摘要

T-Box转录因子5(TBX5)变体与Holt-Oram综合征有关。Holt-Oram 综合征在上肢缺陷、先天性心脏缺陷和心律失常方面表现出表型变异性。为了研究 TBX5 变异与心脏疾病之间的基因型-表型关系,我们对文献进行了系统回顾。通过系统回顾,我们在277名患者中发现了108个与心脏表型相关的TBX5变异。心律失常在有错义变异的患者中更为常见(48% 对 30%,p = 0.009),上肢异常在有蛋白截断变异的患者中更为常见(85% 对 64%,p = 0.0008)。我们发现,T-box 结构域中的错义变异具有聚集性。此外,我们还发现了一个患有房间隔缺损的家族。通过全外显子测序,我们在 TBX5 中发现了一个新的错义变异 p.Phe232Leu。该患者的心脏表型包括房间隔缺损、心律失常、心力衰竭和扩张型心肌病。临床检查发现该患者有轻微的上肢畸形。因此,该家族符合 Holt-Oram 综合征的诊断标准。我们概述了与 TBX5 变体相关的心脏表型,并显示与蛋白截断变体相比,与错义变体相关的心律失常风险更高。我们报告了一个具有非典型 Holt-Oram 综合征表型的家族中的 TBX5 新型错义变异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TBX5 variants and cardiac phenotype: A systematic review of the literature and a novel variant

T-Box Transcription Factor 5 (TBX5) variants are associated with Holt-Oram syndrome. Holt-Oram syndrome display phenotypic variability, regarding upper limb defects, congenital heart defects, and arrhythmias. To investigate the genotype-phenotype relationship between TBX5 variants and cardiac disease, we performed a systematic review of the literature. Through the systematic review we identified 108 variants in TBX5 associated with a cardiac phenotype in 277 patients. Arrhythmias were more frequent in patients with a missense variant (48% vs 30%, p = 0.009) and upper limb abnormalities were more frequent in patients with protein-truncating variants (85% vs 64%, p = 0.0008). We found clustering of missense variants in the T-box domain. Furthermore, we present a family with atrial septal defects. By whole exome sequencing, we identified a novel missense variant p.Phe232Leu in TBX5. The cardiac phenotype included atrial septal defect, arrhythmias, heart failure, and dilated cardiomyopathy. Clinical examination revealed subtle upper limb abnormalities. Thus, the family corresponds to the diagnostic criteria of Holt-Oram syndrome.

We provide an overview of cardiac phenotypes associated with TBX5 variants and show an increased risk of arrhythmias associated to missense variants compared to protein-truncating variants. We report a novel missense variant in TBX5 in a family with an atypical Holt-Oram syndrome phenotype.

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来源期刊
CiteScore
4.10
自引率
0.00%
发文量
193
审稿时长
66 days
期刊介绍: The European Journal of Medical Genetics (EJMG) is a peer-reviewed journal that publishes articles in English on various aspects of human and medical genetics and of the genetics of experimental models. Original clinical and experimental research articles, short clinical reports, review articles and letters to the editor are welcome on topics such as : • Dysmorphology and syndrome delineation • Molecular genetics and molecular cytogenetics of inherited disorders • Clinical applications of genomics and nextgen sequencing technologies • Syndromal cancer genetics • Behavioral genetics • Community genetics • Fetal pathology and prenatal diagnosis • Genetic counseling.
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