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
Affiliations
Xia Li
Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
Weizhe Shi
Department of Pediatric Orthopedics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
Xuejiao Ding
Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
Jingchun Li
Department of Pediatric Orthopedics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
Yiqiang Li
Department of Pediatric Orthopedics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
Jianping Wu
Department of Pediatric Orthopedics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
Zhe Yuan
Department of Pediatric Orthopedics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
Tianying Nong
Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
Hongwen Xu
Department of Pediatric Orthopedics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China; Corresponding author.
Mingwei Zhu
Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China; Corresponding author.
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.
