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Published on: August 15, 2019
Familial hypertrophic cardiomyopathy associated with TBX1 variation
Jie Zhang1, Yafei Deng1, Yaxin Huang1
1Department of Medical Genetics, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, PR China.
Insights
A novel mutation in the T-box transcription factor 1 (TBX1) gene was identified as a cause of hypertrophic cardiomyopathy (HCM) in a Chinese family. This finding establishes a new genetic link between TBX1 and HCM.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Molecular Biology
Background:
- Hypertrophic cardiomyopathy (HCM) is a prevalent genetic cardiovascular disease with diverse genetic causes.
- The T-box transcription factor 1 (TBX1) gene is known for its role in congenital cardiovascular defects but has not been previously linked to HCM.
Purpose of the Study:
- To investigate the genetic basis of hypertrophic cardiomyopathy (HCM) in a Chinese family.
- To identify novel gene mutations associated with HCM.
- To explore the potential role of the TBX1 gene in HCM pathogenesis.
Main Methods:
- Whole-exome sequencing (WES) was utilized to detect mutations in affected family members.
- Sanger sequencing confirmed the identified mutation and assessed familial co-segregation.
- A comprehensive literature review analyzed existing data on TBX1 mutations and phenotypes.
Main Results:
- A novel heterozygous frameshift mutation in the TBX1 gene (NM_080647.1:c.3_27dup, p.Met10Alafs∗167) was discovered in individuals with HCM.
- Segregation analysis confirmed a strong correlation between the TBX1 mutation and the HCM phenotype within the family.
- This study represents the first report linking TBX1 mutations to hypertrophic cardiomyopathy.
Conclusions:
- Familial hypertrophic cardiomyopathy (HCM) is identified as a novel phenotype associated with TBX1 gene mutations.
- These findings broaden the known spectrum of TBX1 mutations and their related clinical manifestations.
- Further research is warranted to elucidate the molecular mechanisms underlying TBX1-associated HCM.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
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