Holt-Oram syndrome: clinical and molecular description of 78 patients with TBX5 variants
Holt-Oram syndrome: clinical and molecular description of 78 patients with TBX5 variants
复制标题
DOI：
10.1038/s41431-018-0303-3
复制
发表时间：
2019-03-01
影响因子：
5.2
通讯作者：
Petit, Florence
中科院分区：
文献类型：
--
作者：
Vanlerberghe, Clemence;Jourdain, Anne-Sophie;Petit, Florence
Holt-Oram综合征（HOS）是一种常染色体显性遗传疾病，其特征为先天性心脏病（CHD），伴或不伴节律紊乱和桡骨缺损，由TBX 5变体引起。该诊断受到表达变异性和与其他疾病如Okihiro综合征、TAR综合征或Fanconi病的大量表型重叠的挑战。我们回顾性分析了2002年至2014年间因怀疑HOS而转诊的212例患者，这些患者接受了TBX 5筛查。在78名患者中发现了TBX 5变体，这是迄今为止描述的最大分子系列。在该队列中，61人符合先前描述的诊断标准，17人被认为具有不确定的HOS诊断。91%的TBX 5变异患者存在CHD，房间隔缺损是最常见的（61.5%）。基因型-表型研究强调了HOS中一些关键特征的重要性：CHD的间隔特征、桡骨缺损的双侧和不对称特征以及肩或肘关节活动性缺损的存在。此外，21例患者出现重叠情况。其中13间公司的简介属典型的居屋计划。我们讨论了可以采取的策略，以改善其余典型患者的分子描绘。
Holt-Oram syndrome (HOS) is an autosomal dominant condition characterised by the association of congenital heart defect (CHD), with or without rhythm disturbances and radial defects, due to TBX5 variants. The diagnosis is challenged by the variability of expression and the large phenotypic overlap with other conditions, like Okihiro syndrome, TAR syndrome or Fanconi disease. We retrospectively reviewed 212 patients referred for suspicion of HOS between 2002 and 2014, who underwent TBX5 screening. A TBX5 variant has been identified in 78 patients, representing the largest molecular series ever described. In the cohort, 61 met the previously described diagnostic criteria and 17 have been considered with an uncertain HOS diagnosis. A CHD was present in 91% of the patients with a TBX5 variant, atrial septal defects being the most common (61.5%). The genotype-phenotype study highlights the importance of some critical features in HOS: the septal characteristic of the CHD, the bilateral and asymmetric characteristics of the radial defect and the presence of shoulder or elbow mobility defect. Besides, 21 patients presented with an overlapping condition. Among them, 13 had a typical HOS presentation. We discuss the strategies that could be adopted to improve the molecular delineation of the remaining typical patients.