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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.
Subject(s)
Humans , Male , Female , Adolescent , T-Box Domain Proteins/genetics , East Asian People , Breast Diseases/genetics , MutationABSTRACT
Objective : To explore the role of over-expression of TBX3 and TBX18 in inducing human induced pluripotent stem cells (HiPS) to enrich and differentiate into sinoatrial node-like cells. Methods: The expression of stemness markers OCT3/4, SOX2, and NANOG in HiPS was detected by real-time fluorescence quantitative PCR (qRT- PCR), and compared with human embryonic stem cells (hESCs). Immunofluorescence staining was used to observe the expression of HiPS stemness markers OCT3/4, NANOG, SSEA4, and TRA-1-60. The HiPS were directional differentiated into cardiomyocytes, the expressions of ISL1, NK2 homeobox 5 (NKX2-5), ACTN1, and TNNT2 were detected by qRT-PCR, and human adult cardiomyocytes (hACM) were used as positive control. Immunofluorescence staining was used to observe the expressions of NKX2-5, cardiac troponin (cTnT), α-actinin, atria myosin light chain 2A (MLC-2A), and ventricular myosin light chain 2V (MLC-2V). The positive rate of α-actinin was detected by flow cytometry. On the 3rd day after HiPS were differentiated into cardiomyocytes (mesodermal stage), lentiviral over-expressions of sinoatrial node-related genes TBX3 and TBX18 were carried out for 21 days. The relative expressions of specific markers TBX3, TBX18, SHOX2, NKX2-5, HCN4, and HCN1 in sinoatrial node cells were detected by qRT-PCR, and compared with enhanced green fluorescent protein blank virus. Results : OCT3/4, SOX2, and NANOG were highly expressed in HiPS and ESCs, and there was no significant difference in the relative expression of each gene ( P>0.05); OCT3/4 and NANOG were specifically distributed in the nucleus of HiPS, while SSEA4 and TRA-1-60 were distributed in the cell membrane. The relative expressions of ISL1 gene at 5, 7, 21, and 28 days and NKX2-5 gene at 7, 21, and 28 days of HiPS differentiation into cardiomyocytes were significantly higher than those of hACM ( P0.05). There was no significant difference in the relative expression of each gene between the over-expressed TBX18 group and the control group ( P>0.05). Conclusion: HiPS and hESCs have similar pluripotency, and we have established a stable method for maintaining and culturing the stemness of HiPS. A technological platform for the efficient differentiation of HiPS into cardiomyocytes has been successfully established. Although TBX3 and TBX18 do not play a significant role in promoting the enrichment and differentiation of HiPS into sinoatrial node-like cells, TBX3 shows a certain promoting trend, which can be further explored in the future.
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Objective To investigate the molecular mechanisms of PLCεin regulating the invasion and migration of human bladder cancer cells in vitro.Methods After cells treated with recombinant adenovirus , the migratory/in-vasive abilities of T24 cells were explored by wound healing and Transwell chamber cell migration and invasion as -say;RT-PCR was used to detect the mRNA levels of PLCε;The protein levels of PLCε,PKCα,PKCβ, TBX3 and E-cadherin were determined by Western blot;QRT-PCR was used to detect the mRNA levels of TBX3 and E-cad-herin.Results It was confirmed by digesting and sequencing that the recombinant adenovirus had been constructed successfully .The expression of PLCε mRNA and PLCε protein were both decreased after the infection of Ad-shPLCε.Wound healing and Transwell chamber cell migration/invasion assay showed that Ad-shPLCε treatment could inhibit the migratory and invasive activity of bladder cancer cells(P<0.05).The results of Western blot indicated that the expression of PKCα/βin membrane decreased ( P<0.05 ) , and phosphorylation level of PKCαand PKCβwas reduced .QRT-PCR and Western blot analysis demonstrated that the expression level of TBX 3 de-creased , but the expression level of E-cadherin increased .Conclusions PLCε shRNA can inhibit migratory and invasive ability of bladder cancer cells through PKCα/β/TBX3/E-cadherin pathway .
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As a member of T-box family,Tbx3 (T-box3) is widely expressed in multiple organs and involves in the development of breast,limb,heart,eye,lung and pancreas during embryonic development stage.Moreover,Tbx3 plays an important role in maintaining the embryonic stem cells.Recent studies show that Tbx3 can work as a transcription factor to participate in the initiation and progression of tumor by epithelialmesenchymal transition,induction tumor stemness and methylation.A better understanding of Tbx3 will provide new insights into genetic diagnosis and targeted treatment of tumor.
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Objective To clarify the expression of Tbx3 gene in breast cancer tissues and its clinical significance, and the expression of Tbx3 gene in different clinical pathological characteristic breast cancer. Methods Expression of Tbx3 gene in 53 specimens of breast cancer and 28 specimens of normal breast tissues were investigated by immunohistochemistry, analysing the clinical significance. Meanwhile the correlation of expression of Tbx3 gene in breast cancer classified was investigated by estrogen receptor ( ER),lymph node metastasis, Her-2 status. Results Positive rate of Tbx3 gene in breast cancer tissues was significantly higher than that in normal breast tissues [73.58% (39/53) vs 14.29% (4/28)] (P ＜ 0.05).Positive rate of Tbx3 gene in ER positive breast cancer tissues was higher than that in ER negative breast cancer tissues [ 84.38% (27/32) vs 57.14% ( 12/21 ) ] (P ＜ 0.05 ). Positive rate of Tbx3 gene in breast cancer tissues with lymph node metastasis was higher than that in breast cancer tissues without lymph node metastasis [86.21%(25/29) vs 58.33% (14/24) ] (P ＜ 0.05). Positive rate of Tbx3 gene in Her-2 positive breast cancer tissues was higher than that in Her-2 negative breast cancer tissues[ 93.75%(15/16) vs 64.86% (24/37) ] (P ＜ 0.05). Conclusions Tbx3 gene is over expressed in breast cancer tissues. It is related to ER, lymph node metastasis, Her-2 status.
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Objective To explore the role of Tbx3 gene in the occurrence and development of breast cancer. Methods 44 cases of the fresh breast carcinoma tissues and peritumor tissues were collected individually, the gene expression of Tbx3 was detected by RT PCR and the relationship between the changes of Tbx3 gene expression and the related clinicopathological factors of breast carcinoma was investigated. Results Obviously, the expression level of Tbx3 gene in breast carcinoma tissues was higher than that in the peritumor tissues. Furthermore, Tbx3 gene expression level in breast carcinoma tissues was not associated with the tumor size and ages of patients. However, the histological grading of breast carcinoma, tumor infiltrating degree, TNM stagings, and axillary lymph node metastasis were positively correlated with the expression level of Tbx3 gene. Conclusion Tbx3 gene with high expression may promote the occurrence and development of breast cancer and it is also likely a symbol of crucial changes in the development of breast cancer