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.

SUBMITTER: Li X 

PROVIDER: S-EPMC9699963 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature