OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with congenital isolated adrenocorticotropic hormone deficiency (IAD). METHODS: Clinical characteristics of the patient was reviewed. Genomic DNA of the child was subjected to whole exome sequencing. RESULTS: Genetic testing has confirmed the diagnosis of congenital IAD by identification of compound heterozygous variants of the TBX19 gene, which included a pathogenic nonsense c.535C>T (p.R179X) variant inherited from his father and a novel missense c.298C>T (p.R100C) variant inherited from his mother. CONCLUSION Congenital IAD due to variants of the TBX19 gene is a rare autosomal recessive disease. It is characterized by low plasma adrenocorticotropic hormone and cortisol levels but normal levels of other pituitary hormones. Delayed diagnosis may lead to severe early-onset adrenal failure and wrong treatment which may result in neonatal mortality. Hydrocortisone replacement is effective. Detection of pathogenic variant of TBX19 gene is the key to diagnosis.
Adrenal Insufficiency/genetics* ; Child ; Homeodomain Proteins/genetics* ; Humans ; T-Box Domain Proteins/genetics*

Ulnar-Mammary syndrome (UMS) is a rare monogenic disorder caused by mutations of the TBX3 gene. This paper reported a family of UMS. The proband, a 15-year old man, was presented with mammary gland dysplasia, ulnar limb defect, short stature, and delayed growth. Whole exome sequencing revealed a 1294_1301dup mutation in exon 6 of the TBX3 gene. Sanger sequencing was used to verify other members of the family, which suggested his mother also carried the same mutation, but merely resulting in the dysplasia of her left little finger. Notably, unilateral finger involvement without any systemic organ involvement was unusual in UMS patients. The proband then was treated with recombinant human growth hormone (rhGH) and human chorionic gonadotropin (hCG). After a year and a half, his height and secondary sexual characteristics were significantly improved. The clinical manifestations of the disease are highly heterogeneous, which is easy to be misdiagnosed and missed. When the diagnosis is unclear, genetic testing is helpful for auxiliary diagnosis.
Humans ; Male ; Female ; Adolescent ; T-Box Domain Proteins/genetics* ; East Asian People ; Breast Diseases/genetics* ; Mutation

Animals ; DNA, Fungal ; Phosphorylation ; RNA Polymerase II ; Sequence Homology, Nucleic Acid ; T-Box Domain Proteins ; genetics

The T-Box transcription factor family plays a crucial role during heart development. A large amount of clinical evidence showed TBX 1, 2, 5, 18, 20 proteins to be strongly associated with human congenital heart diseases including atrial septal defect, mitral valve disease, and tetralogy of Fallot. Among these, TBX20 has attracted much attention. This article gives a brief review for the progress made in the research on TBX20 and cardiovascular disease.
Cardiovascular Diseases ; prevention & control ; Gene Expression Regulation ; Humans ; T-Box Domain Proteins ; genetics

OBJECTIVETo explore the role of TBX3 gene in the pathogenesis of breast cancer.

METHODSThe total RNA of 51 fresh breast cancer tissues and the corresponding adjacent tissues were extracted and reverse transcribed into cDNA to detect the expression of TBX3 mRNA by real-time PCR. The correlation between TBX3 mRNA expression and the clinicopathologic parameters in relation to breast cancer metastasis was analyzed.

RESULTCompared to that in the adjacent tissues, the expression of TBX3 mRNA was markedly increased in breast cancer tissues. TBX3 mRNA expression was significantly higher in metastatic breast cancer than in non-metastatic tumors.

CONCLUSIONIncreased expression of TBX3 mRNA suggests the involvement of TBX3 in the pathogenesis and metastasis of breast cancer.

Breast Neoplasms ; etiology ; genetics ; pathology ; Female ; Humans ; Neoplasm Metastasis ; genetics ; RNA, Messenger ; genetics ; metabolism ; T-Box Domain Proteins ; genetics ; metabolism

Cardiac valves are highly organized yet delicate structures that ensure unidirectional blood flow through the cardiac chambers and large vessels. Disturbed development of cardiac valves can lead to aberrant heart formation and function which account for approximately one third of congenital heart diseases. The formation of cardiac valves is a dynamic process accomplished by a series of complex events including lineage determination and cell proliferation, differentiation and migration. This paper reviews current knowledge about the role of Tbx20 gene in the development of cardiac valves, which include functional diversities of Tbx20 at various stages of cardiac valve development, its interaction with other signaling pathways, and genetic network involved in endocardial development.
Cell Differentiation ; Cell Proliferation ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Heart Valves ; embryology ; Humans ; T-Box Domain Proteins ; genetics

OBJECTIVETo explore the differences of NKX2.5 and TBX5 gene mutations between in vitro fertilization (IVF) children with congenital heart disease (CHD) and naturally conceived children with CHD.

METHODSBlood samples from 68 IVF children with CHD and 98 naturally conceived children with CHD were collected. The mutations in coding regions 1 and 2 of the NKX2.5 gene, and coding regions 4, 5, and 8 of the TBX5 gene were examined by polymerase chain reaction (PCR) and DNA sequencing.

RESULTSAn A-to-G mutation at nucleotide 63 (c.63A>G) in coding region 1 of the NKX2.5 gene was found in both IVF and naturally conceived children with CHD. There were no significant differences in genotype and allele frequencies at c.63A>G locus of the NKX2.5 gene between the two groups. No mutations were detected in coding region 2 of the NKX2.5 gene and coding regions 4, 5 and 8 of the TBX5 gene.

CONCLUSIONSThere is no difference in NKX2.5 and TBX5 gene mutations between IVF and naturally conceived children with CHD. Therefore, it is presumed that assisted reproductive technology may not lead to mutations in the NKX2.5 and TBX5 genes.

Child, Preschool ; Female ; Fertilization in Vitro ; Heart Defects, Congenital ; genetics ; Homeobox Protein Nkx-2.5 ; genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; T-Box Domain Proteins ; genetics

OBJECTIVE: To describe a family with intellectual developmental disorder with autism and speech delay (IDDAS) caused by a splice variant of TBR1 gene. METHODS: A pregnant women with mental retardation, who also had a family history of mental retardation, was admitted to Prenatal Diagnosis Center of WanBei Coal and Electricity Group General Hospital Corporation in April 2019. Molecular genetic tests were performed on the pregnant women and ten other family members to analyze the pathogenic genotype. Functional assays of the pathogenic variant was carried out by minigene technology. With the determination of the genotype, prenatal diagnosis was carried out by amniotic fluid sampling. RESULTS: Through whole exome sequencing, a novel splicing variant (c.1129-1G>C) was identified in the TBR1 gene of the proband, which has co-segregated with the disease phenotype in the family. The results of minigene assay showed abnormal splicing of exon 5. The variant was not detected in the fetal amniotic fluid. Fetal growth and development were normal one year after the birth. CONCLUSION The c.1129-1G>C variant of the TBR1 probably underlay the disease in of the pedigree. Timely prenatal genetic diagnosis and consultation can help to stop the transmission of the pathogenic variant.
Autistic Disorder/genetics* ; China ; Developmental Disabilities ; Female ; Humans ; Infant ; Intellectual Disability/genetics* ; Language Development Disorders ; Pedigree ; Pregnancy ; T-Box Domain Proteins/genetics*

The early cardiac biological pacemaker studies were mostly around HCN channel, and how to build a biological pacemaker through the enhanced If current. In recent years, however, people found that the genes of Tbx3 could play an important role in the development of cardiac conduction system, especially in processes of the maturity of the sinoatrial node and maintenance of its function. And the Tbx3 can further optimize the biological pacemaker. Therefore, it could be a new therapeutic focus in biological pacemaker and treatment of cardiac conduction system disease. This paper summarizes some of the latest research progress of the Tbx3 in biological pacemaker in recent years. We hope that this review could provide theoretical basis for the clinical applications of Tbx3.
Arrhythmias, Cardiac ; genetics ; Biological Clocks ; Brugada Syndrome ; Cardiac Conduction System Disease ; Heart ; physiopathology ; Heart Conduction System ; abnormalities ; Humans ; Sinoatrial Node ; T-Box Domain Proteins ; genetics

The aim of this study is to clone the mouse T-bet promoter and enhancer, construct and identify the firefly luciferase reporter gene plasmid pGL4.10-TBX21pr-CNS for T-bet transcription regulation study and its function in signaling of multiple sclerosis. The promoter and CNS of T-bet were predicted by bioinformatics assay. The predicted fragment of mouse T-bet promoter plus CNS was amplified by PCR and cloned into pGL4.10. The recombinant plasmid pGL4.10-TBX21pr-CNS was transferred into Escherichia coli DH5α. The positive clone was identified by double digestion with Kpn I and Sfi I and DNA sequencing. Finally, pGL4.10-TBX21pr-CNS was cotransfected with pRL-TK into 293T cells and Jurkat cells, pRL-TK and pGL4.10 as a control. The luciferase activity in 293T cells (P = 0.012 2) and Jurkat cells (P = 0.002 2) was higher than that of the control group. A fragment of 1 028 bp mouse T-bet promoter plus 1 308 bp CNS was successfully cloned and the firefly luciferase reporter gene plasmid pGL4.10-TBX21pr-CNS was constructed. In 293T cells and Jurkat cells, pGL4.10-TBX21pr-CNS has the promoter functions. This work offers a basic material for the research of T-bet transcription.
Animals ; Gene Expression Regulation ; Genes, Reporter ; Genetic Vectors ; Luciferases ; Mice ; Multiple Sclerosis ; Plasmids ; Promoter Regions, Genetic ; T-Box Domain Proteins ; genetics