Bamshad M, Lin R C, Law D J, Watkins W C, Krakowiak P A, Moore M E, Franceschini P, Lala R, Holmes L B, Gebuhr T C, Bruneau B G, Schinzel A, Seidman J G, Seidman C E, Jorde L B
Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.
Nat Genet. 1997 Jul;16(3):311-5. doi: 10.1038/ng0797-311.
Ulnar-mammary syndrome is a rare pleiotropic disorder affecting limb, apocrine gland, tooth and genital development. We demonstrate that mutations in human TBX3, a member of the T-box gene family, cause ulnar-mammary syndrome in two families. Each mutation (a single nucleotide deletion and a splice-site mutation) is predicted to cause haploinsufficiency of TBX3, implying that critical levels of this transcription factor are required for morphogenesis of several organs. Limb abnormalities of ulnar-mammary syndrome involve posterior elements. Mutations in TBX5, a related and linked gene, cause anterior limb abnormalities in Holt-Oram syndrome. We suggest that during the evolution of TBX3 and TBX5 from a common ancestral gene, each has acquired specific yet complementary roles in patterning the mammalian upper limb.
尺骨-乳腺综合征是一种罕见的多效性疾病，会影响肢体、顶泌汗腺、牙齿和生殖器的发育。我们证明，人类T-box基因家族成员TBX3的突变在两个家族中导致了尺骨-乳腺综合征。每个突变（一个单核苷酸缺失和一个剪接位点突变）预计会导致TBX3单倍剂量不足，这意味着该转录因子的关键水平是几个器官形态发生所必需的。尺骨-乳腺综合征的肢体异常涉及后部结构。相关且连锁的基因TBX5的突变会导致 Holt-Oram综合征中的前肢异常。我们认为，在TBX3和TBX5从共同祖先基因进化的过程中，它们各自在哺乳动物上肢模式形成中获得了特定但互补的作用。
