Mutations in the human TBX4 gene cause small patella syndrome
Mutations in the human TBX4 gene cause small patella syndrome
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DOI：
10.1086/421331
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发表时间：
2004-06-01
影响因子：
9.8
通讯作者：
van Bokhoven, H
中科院分区：
文献类型：
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作者：
Bongers, EMHF;Duijf, PHG;van Bokhoven, H
小髌骨综合征 (SPS) 是一种常染色体显性遗传性骨骼发育不良，其特征是髌骨发育不全或发育不全以及骨盆和足部异常，包括坐骨和耻骨下支骨化破坏。我们通过单倍型分析确定了染色体 17q22 上 5.6 cM 的 SPS 关键区域。在 6 个 SPS 家族的编码 T 盒蛋白 4 (TBX4) 的位置基因中发现了推定的功能丧失突变。 TBX4 编码的转录因子具有高度保守的 DNA 结合 T 盒结构域，已知该结构域在鸡和小鼠的下肢发育中发挥着至关重要的作用。目前在 SPS 患者中鉴定出杂合 TBX4 突变，以及缺乏 Tbx4 的动物的相似骨骼表型，确定了 TBX4 在人类下肢和骨盆发育途径中的重要性。
Small patella syndrome (SPS) is an autosomal-dominant skeletal dysplasia characterized by patellar aplasia or hypoplasia and by anomalies of the pelvis and feet, including disrupted ossification of the ischia and inferior pubic rami. We identified an SPS critical region of 5.6 cM on chromosome 17q22 by haplotype analysis. Putative loss-of-function mutations were found in a positional gene encoding T-box protein 4 (TBX4) in six families with SPS. TBX4 encodes a transcription factor with a strongly conserved DNA-binding T-box domain that is known to play a crucial role in lower limb development in chickens and mice. The present identification of heterozygous TBX4 mutations in SPS patients, together with the similar skeletal phenotype of animals lacking Tbx4, establish the importance of TBX4 in the developmental pathways of the lower limbs and the pelvis in humans.