Literature review, report, and analysis of genotype and clinical phenotype of a rare case of ulnar-mammary syndrome.

Objective: The clinical characteristics of Ulnar-mammary syndrome (UMS) caused by mutations in TBX3 (T-Box transcription factor 3) were studied and the correlation between genotype and clinical phenotype were analyzed to improve awareness and early diagnosis of the disease. Methods: The clinical data of a boy aged 13 years and 5 months with left forearm deformity and growth retardation as the main features were analyzed. Genomic exon detection was performed, and the results were verified by Sanger sequencing. Simultaneously, we performed literature review to analyze the correlation between clinical phenotypes and genotypes. Results: The clinical manifestations in the child were short stature, ulnar hypoplasia of the forearm, hypohidrosis, retracted nipple, micropenis, and cryptorchidism. Laboratory examination revealed hyperthyroidism, growth hormone deficiency, and hypogonadotropic hypogonadism. Imaging results displayed delayed bone age, small pituitary gland, and persistence of Rathke's cleft cyst. The results of the exome sequencing revealed the deletion of AGA at positions 1121-1,124 of TBX3, which resulted in a frameshift mutation (c.1121-1124del AGAG; pGlu374fs). According to the American College of Medical Genetics (ACMG) assessment, the mutation is a pathogenic variant. A definitive diagnosis of UMS was made on the basis of the clinical phenotype of the patient. The Chinese and English literature were reviewed to analyze the correlation between TBX3 genotype and clinical phenotype. Conclusion: UMS is a rare hereditary disease caused by mutations in TBX3. There is significant clinical heterogeneity associated with the variants of this gene. To our knowledge, this mutation site in TBX3 has been reported for the first time, thereby expanding the mutation spectrum of this gene.

Ulnar-Mammary syndrome with TBX3 gene mutation in a Chinese family: A case report and literature review. / TBX3åŸºå› çªå˜è‡´Ulnar-Mammary综合征1ä¾‹å®¶ç³»æŠ¥é“å¹¶æ–‡çŒ®å¤ä¹ .

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.

Ulnar-Mammary syndrome with TBX3 gene mutation in a Chinese family: A case report and literature review / 中南大学学报(医学版)

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.

A novel A > G polymorphism in the intron 2 of TBX3 gene is significantly associated with body size in donkeys.

T-box transcription factor 3 (TBX3) gene encodes a transcriptional suppressor and plays an important role in embryonic development, which belongs to the T-box family. TBX3 also has been found to be associated with body size traits in horse that is a relative of donkey. Therefore, TBX3 is considered as a promising candidate gene for economic traits of donkey. This study aimed to reveal the significant variation of TBX3 gene in Dezhou donkey and explores the relationship between genotypes and body sizes. In this study, an A > G mutation was found in the intron 2 of TBX3 gene by sequencing, and three genotypes (AA, GG and AG) were identified in 380 Dezhou donkey individuals with Tm-shift method. Association analysis illustrated that there were significant differences between AA and GG genotype in body length, body height, chest depth, chest circumference, body weight, hucklebone width and rump length. Our results demonstrated that the polymorphism of TBX3 is significantly associated with body size traits, which can serve as a marker to improve donkey production performance.

Expression level of TBX3 gene in renal carcinoma and its clinical significance.

The aim of the current study was to investigate and discuss the function of T-box 3 (TBX3) gene expression in the pathogenesis of renal carcinoma. The carcinoma, adjacent and normal renal tissues of 210 patients with renal carcinoma who presented to The Central Hospital of Wuhan, Tongji Medical College from March, 2006 to March, 2012 were collected to extract total RNAs. The total RNAs were reverse-transcribed into complementary DNA (cDNA), and quantitative polymerase chain reaction (qPCR) was applied to detect the expression of TBX3 gene in these tissues, followed by its association with the prognosis of renal carcinoma as well as clinical features. A comparison of the renal carcinoma tissues with the adjacent tissues showed that TBX3 gene was obviously highly expressed in renal carcinoma tissues (P<0.05). In addition, compared with normal renal tissues, TBX3 gene was obviously highly expressed in renal carcinoma tissues (P<0.05). There was no significant difference in the expression levels of TBX3 gene in normal renal tissues and adjacent tissues (P=0.15). The expression of TBX3 gene in renal carcinoma tissues was not associated with patient age, sex and tumor size (P>0.05), but it was associated with tumor-node-metastasis (TNM) staging and lymph node metastasis (P<0.05). The Kaplan-Meier survival analysis revealed that the median survival time of patients in the positive TBX3 gene expression group (37.5 months) was shorter than that in the negative TBX3 gene expression group (66 months), and there was a statistical difference (P<0.05). The 3- and 5-year survival rates in the negative TBX3 gene expression group were 74 and 62%, respectively, and the 3- and 5-year survival rates in the positive TBX3 gene expression group were 52 and 32%, respectively, and the differences were significant (P<0.05). The results suggest that TBX3 gene is highly expressed in renal carcinoma tissues, and it is associated with TNM staging, lymph node metastasis and distant metastasis, which may be involved in the occurrence and metastasis of renal carcinoma.

Life-threatening cardiac episode in a Polish patient carrying contiguous gene microdeletion of the TBX5 and the TBX3 genes.

Holt-Oram syndrome (HOS) features radial ray hypoplasia, heart defect and cardiac conduction impairment. Ulnar-mammary syndrome (UMS) characterizes congenital defects of the ulnar side of the upper limbs, underdevelopment of apocrine glands including hypoplasia and the dysfunction of mammary glands, hypogonadism and obesity. Inheritance of both conditions is autosomal dominant, mutations or deletions are found in the TBX5 and TBX3 gene, respectively. The Polish patient presented short stature, obesity, congenital malformation of the radial and ulnar side of the upper limbs, heart block, hypogonadism and dysmorphic features. At the age of 13 years he lost consciousness developing respiratory insufficiency caused by bradycardia in the course of sudden atrioventricular third degree heart block requiring immediate implantation of pace maker-defibrillator device. Microdeletion of the 12q24.21 was identified using array CGH method. This region includes contiguous genes the TBX5, TBX3, and part of RBM19. The patient initially diagnosed as having HOS, was found to present the UMS features as well. Array CGH method should be applied in patients suspected of HOS or UMS, especially when sequencing of TBX5 or TBX3 genes fails to identify causative mutation.