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

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

• Holt–Oram syndrome
• Common atrium
• Whole exome sequencing
• TBX5
• Novel mutation