PDF(Pubmed)
Abstract：
Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder characterized by skeletal abnormalities of the upper limbs and often cardiac malformations. We investigated a Chinese family with clinical features suggestive of HOS. Clinical examinations revealed that both the proband and his father had anomalies in the upper limbs and heart. The proband had a rare common atrium. Whole exome sequencing detected a novel small-insertion mutation (c.680_681insCTGAGAATAAT; p.Ile227fs∗) in TBX5 gene, the known disease gene for HOS. The mutation cosegregated with HOS phenotypes in the family and was predicted to cause frameshift, resulting in a truncated protein. In this study, we described a rare HOS case with common atrium. A novel small-insertion in TBX5 coding sequence was identified and speculated to be the disease-causing genetic variant in the family. Our finding expands the clinical feature spectrum and genetic aetiology spectrum of HOS.
摘要：
Holt-Oram综合征（HOS）是一种罕见的常染色体显性遗传病，其特征是上肢骨骼异常，通常是心脏畸形。我们调查了一个具有提示居屋的临床特征的中国家庭。临床检查显示，先证者和他的父亲上肢和心脏都有异常。先证者有罕见的心房。全外显子组测序在TBX5基因中检测到一种新的小插入突变（c.680_681insCTGAGAATAAT;p.Ile227fs*），已知的HOS疾病基因。该突变与家族中的HOS表型分离，并预测会导致移码，导致截短的蛋白质。在这项研究中,我们描述了一个罕见的有共同心房的居屋个案。鉴定了TBX5编码序列中的新小插入，并推测是该家族中引起疾病的遗传变异。我们的发现扩展了HOS的临床特征谱和遗传病因谱。
