This report describes ulnar-mammary syndrome, autosomal dominant disorder characterized by posterior limb deficiencies or duplications, and apocrine/mammary gland hypoplasia. The human gene implicated is TBX3, which encodes a transcription factor with T-box DNA-binding domain. There is one moderate-scoring fly ortholog, Dmel\bi, for which multiple genetic reagents, including loss of function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Multiple UAS constructs of the human gene Hsap\TBX3 have been introduced into flies, including wild-type constructs, and constructs bearing variants associated with human disease. See the 'Disease-Implicated Variants' table below.
Ubiquitous overexpression of wild-type or mutant Hsap\TBX3 results in lethality at the larval/pupal transition. Overexpression wild-type or mutant Hsap\TBX3 under the control of eye-specific drivers that express prior to morphogenetic furrow formation is also lethal, with a few viable escapers with reduced or absent eyes. Eye-specific expression at later stages is adult-viable, with ommatidial defects. Wing disc-specific expression of wild-type or mutant Hsap\TBX3 results in lethality and/or severe wing defects.
[updated Jan. 2025 by FlyBase; FBrf0222196]
[ULNAR-MAMMARY SYNDROME; UMS](https://omim.org/entry/181450)
[T-BOX TRANSCRIPTION FACTOR 3; TBX3](https://omim.org/entry/601621)
Ulnar-mammary syndrome (UMS) is an autosomal dominant disorder characterized by posterior limb deficiencies or duplications, apocrine/mammary gland hypoplasia and/or dysfunction, abnormal dentition, delayed puberty in males, and genital anomalies (Bamshad et al., 1996, pubmed:8923944]). [from MIM:181450; 2025.01.27]
Ulnar-mammary syndrome (UMS) is caused by heterozygous mutation in the TBX3 gene on chromosome 12q24. [from MIM:181450; 2025.01.27]
TBX3 is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This protein is a transcriptional repressor and is thought to play a role in the anterior/posterior axis of the tetrapod forelimb. [provided by RefSeq, Jul 2008]
The TBX3 gene is a member of a family of transcription factors that share a T-box DNA-binding domain (summary by Meneghini et al., 2006, pubmed:16530712]). [from MIM:601621; 2025.01.27]
Two to one (2 human to 1 Drosophila); GRM1 has moderate-scoring Drosophila ortholog, bi.
Moderate-scoring ortholog of human TBX3 and TBX2 (1 Drosophila to 2 human).
