Association of single nucleotide polymorphisms of TBX5 gene and environmental exposure index with susceptibility to oral cancer / 中华预防医学杂志

Objective@#To explore the association of TBX5 polymorphisms and environmental exposure index with susceptibility to oral cancer.@*Methods@#A case-control study was conducted to collect 300 oral cancer patients hospitalized in the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University from September 2010 to December 2016. A total of 445 non-tumor patients were selected as the control group. Questionnaires were used to collect the information of all subjects and 5 ml peripheral blood was collected to detect single nucleotide polymorphisms (SNPs) of the rs10492336 locus of TBX5 gene. According to the environmental exposure index score, subjects were divided into two groups, low risk group (0-2.31) and high risk group (2.32-11.76). To analyze the association of TBX5 gene rs10492336 SNPs, environmental exposure index and oral cancer and its interactions.@*Results@#The age of all subjects in the case group and control group were (56.19±13.10) years and (54.56±12.48) years old. Compared with CC genotype, the OR (95%CI) values of the co-dominant genetic model AC genotype and the dominant genetic model AC+AA genotype were 0.69 (0.49-0.98) and 0.70 (0.51-0.97), respectively. Compared with the low risk group, the OR (95%CI) risk of oral cancer in the high risk group was 3.72 (2.55-5.43). The results of gene-environment interaction analysis showed that compared with the group with CC genotype and high risk of environmental exposure index, the OR (95%CI) value of oral cancer in the group with AC+AA genotype and low risk of environmental exposure index was 0.18(0.10-0.31). Furthermore there was a multiplicative interaction between rs10492336 SNPs and environmental exposure index (β=-0.405, P<0.001).@*Conclusion@#This study suggests that the TBX5 gene rs10492336 SNPs and environmental exposure index were associated with oral cancer. And there was a multiplication interaction between rs10492336 SNPs and environmental exposure index.

A Familial Case with Holt-Oram Syndrome with a Novel TBX5 Mutation

Holt-Oram syndrome (HOS) is the most common heart-hand syndrome, which is inherited in an autosomal dominant manner, but most cases are sporadic. This condition is characterized by upper-extremity malformations involving radial-ray, thenar, and carpal bones, and congenital heart malformations including atrial septal defect and ventricular septal defect. It is caused by mutations in the TBX5 gene. In this report, a Korean case with HOS is described, which is inherited from her father. A novel nonsense mutation, p.Glu294*, was identified. This is the first Korean case with HOS confirmed by genetic testing.

A Familial Case with Holt-Oram Syndrome with a Novel TBX5 Mutation

Holt-Oram syndrome (HOS) is the most common heart-hand syndrome, which is inherited in an autosomal dominant manner, but most cases are sporadic. This condition is characterized by upper-extremity malformations involving radial-ray, thenar, and carpal bones, and congenital heart malformations including atrial septal defect and ventricular septal defect. It is caused by mutations in the TBX5 gene. In this report, a Korean case with HOS is described, which is inherited from her father. A novel nonsense mutation, p.Glu294*, was identified. This is the first Korean case with HOS confirmed by genetic testing.

Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome

The Holt-Oram syndrome (HOS) is an autosomal dominant condition characterized by upper limb and cardiac malformations. Mutations in the TBX5 gene cause HOS and have also been associated with isolated heart and arm defects. Interactions between the TBX5, GATA4 and NKX2.5 proteins have been reported in humans. We screened the TBX5, GATA4, and NKX2.5 genes for mutations, by direct sequencing, in 32 unrelated patients presenting classical (8) or atypical HOS (1), isolated congenital heart defects (16) or isolated upper-limb malformations (7). Pathogenic mutations in the TBX5 gene were found in four HOS patients, including two new mutations (c.374delG; c.678G > T) in typical patients, and the hotspot mutation c.835C > T in two patients, one of them with an atypical HOS phenotype involving lower-limb malformations. Two new mutations in the GATA4 gene were found in association with isolated upper-limb malformations, but their clinical significance remains to be established. A previously described possibly pathogenic mutation in the NKX2.5 gene (c.73C > 7) was detected in a patient with isolated heart malformations and also in his clinically normal father.

Genetic Reveal Study of NKX2.5,TBX5 and GATA4 Genes in Patients With Tetralogy of Fallot / 中国循环杂志

Objective:To investigate mRNA expression of cardiac related genes of NKX2.5,TBX5 and GATA4 in patients with tetralogy of fallot(TOF). Methods:A total of 10 TOF patients(TOF group)from 4 months to 8 years with the mean age of 3.5 years were recruited in our hospital from June to December 2005.The patients were diagnosed by typical clinical manifestation and cardiac color echocardiogram, the diagnosis was confirmed by cardiac surgery.6 non-congenital heart disease children were selected as Control group, and they were from 4 months to 9 years with the mean age of 3.8 years.The myocardial total RNA was extracted,the related cDNA was obtained by RT-PCR.The product cDNA was amplified with fluorescent quantitative PCR in order to compare the differences of NKX2.5,TBX5,GATA4 and GAPDH mRNA expression between TOF group and Control group. Results:NKX2.5 mRNA expression in TOF group was statistically decreased than that in Control group,while there were no statistical changes found in TBX5 and GATA4 mRNA expression between TOF group and Control group. Conclusion:The mRNA expression of NKX2.5,TBX5 and GATA4 were found in myocardium development.TOF was possibly related to decreased NKX2.5 mRNA expression.