Novel TBX3 mutation data in families with Ulnar-Mammary syndrome indicate a genotype-phenotype relationship:: mutations that do not disrupt the T-domain are associated with less severe limb defects
Novel TBX3 mutation data in families with Ulnar-Mammary syndrome indicate a genotype-phenotype relationship:: mutations that do not disrupt the T-domain are associated with less severe limb defects
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DOI：
10.1016/j.ejmg.2005.04.021
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发表时间：
2006-03-01
影响因子：
1.9
通讯作者：
Merlo, GR
中科院分区：
文献类型：
--
作者：
Meneghini, V;Odent, S;Merlo, GR
我们描述了一个受尺乳综合征（UMS）影响的家族，其中典型的UMS特征（乳房和腋毛发育不全，上肢和生殖器缺陷）与心脏畸形和肺动脉狭窄一起存在。TBX 3的序列分析显示了一个新的杂合突变，该突变导致外显子6的移码（Nt.1586-1587-insC），导致ORF截短。最近，Tbx 3的表达也已被描述在胚胎鼠心脏的间隔区。这一观察结果可能建立了先天性心脏病与该家族TBX 3突变之间的联系。结合文献中的TBX 3突变数据和这种新突变，我们发现破坏DNA结合结构域的突变与严重上肢畸形和牙齿缺陷的频率较高之间存在关联。一个可能的解释是，保留T结构域的突变TBX 3蛋白，如果翻译，可能在肢体和其他胚胎组织中促进/抑制靶基因转录的活性最低。(c)2005年，Elsevier SAS。All rights reserved.
We describe a family affected by Ulnar-Mammary syndrome (UMS) in which typical UMS traits (hypoplasia of the breast and axillary hair, upper limbs and genital defects) are present together with cardiac malformations and pulmonary stenosis. Sequence analysis of TBX3 shows a new heterozygous mutation that causes a frame-shift (Nt.1586-1587-insC) in exon 6, resulting in a truncated ORF. Recently the expression of Tbx3 has been described also in the septal region of the embryonic murine heart. This observation may establish a link between the congenital heart defects and the TBX3 mutation in this family. Combining the TBX3 mutation data in the literature with this novel mutation we find an association between mutations that disrupt the DNA-binding domain and a higher frequency of severe upper limb malformations and teeth defects. A possible explanation is that mutant TBX3 proteins that retain the T-domain, if translated, might be minimally active in promoting/repressing transcription of target genes in the limbs and in other embryonic tissues. (c) 2005 Elsevier SAS. All rights reserved.