Familial hypertrophic cardiomyopathy associated with TBX1 variation

Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease characterized by significant genetic heterogeneity. While the T-box transcription factor 1 (TBX1) gene is known to cause congenital cardiovascular defects, it has not been previously associated with HCM.

Whole-exome sequencing (WES) was performed to identify causative gene mutations in a recently diagnosed Chinese family with HCM. The mutation was confirmed using Sanger sequencing, which was also employed to investigate familial co-segregation. A literature review was conducted to analyze previously reported TBX1 mutations and their associated phenotypes.

A novel heterozygous frameshift mutation, TBX1 (NM_080647.1):c.3_27dup (p.Met10Alafs∗167), was identified in affected family members. Familial co-segregation analysis revealed that this mutation correlated with the HCM phenotype. To date, no previous studies have reported an association between TBX1 mutations and HCM, suggesting that this may represent a novel TBX1-related phenotype.

This study identifies familial HCM as a new phenotype linked to TBX1 gene mutations. These findings expand the mutation and phenotype spectrum of TBX1 and emphasize the need for further research to understand the mechanisms by which the c.3_27dup (p.Met10Alafs∗167) mutation leads to HCM.