Identification of a novel TBX5 mutation in a Chinese family with rare symptoms of Holt-Oram syndrome

Xia Li; Weizhe Shi; Xuejiao Ding; Jingchun Li; Yiqiang Li; Jianping Wu; Zhe Yuan; Tianying Nong; Hongwen Xu; Mingwei Zhu

doi:10.1016/j.heliyon.2022.e11774

Identification of a novel TBX5 mutation in a Chinese family with rare symptoms of Holt-Oram syndrome

Heliyon. 2022 Nov 21;8(11):e11774. doi: 10.1016/j.heliyon.2022.e11774. eCollection 2022 Nov.

Authors

Xia Li¹, Weizhe Shi², Xuejiao Ding¹, Jingchun Li², Yiqiang Li², Jianping Wu², Zhe Yuan², Tianying Nong¹, Hongwen Xu², Mingwei Zhu¹

Affiliations

¹ Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
² Department of Pediatric Orthopedics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

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.

Keywords: Common atrium; Holt–Oram syndrome; Novel mutation; TBX5; Whole exome sequencing.

Publication types

Case Reports