Braybrook Claire, Lisgo Steven, Doudney Kit, Henderson Deborah, Marçano Ana Carolina B, Strachan Tom, Patton Michael A, Villard Laurent, Moore Gudrun E, Stanier Philip, Lindsay Susan
Institute of Reproductive and Developmental Biology, Imperial College Faculty of Medicine-Hammersmith Campus, Du Cane Road, London W12 ONN, UK.
Hum Mol Genet. 2002 Oct 15;11(22):2793-804. doi: 10.1093/hmg/11.22.2793.
Cleft palate with ankyloglossia (CPX; MIM 303400) is inherited as a Mendelian, semidominant X-linked disorder and has been described in several large families from different ethnic origins. It is a useful genetic model for non-syndromic cleft palate, a common congenital disorder. Recently, the underlying genetic defect in CPX was identified, where unique mutations were found in the T-box-containing transcription factor TBX22. Here we report two new familial cases with novel missense and insertion mutations, each occurring within the T-box domain and highlighting the functional significance of this DNA-binding motif. We describe TBX22 expression in early human development, where expression is found in the palatal shelves and is highest prior to elevation to a horizontal position above the tongue. mRNA is also detected in the base of the tongue in the region of the frenulum that corresponds to the ankyloglossia seen in CPX patients. Other sites of expression include the inferior portion of the nasal septum that fuses to the palatal shelves, the mesenchyme from which tooth buds develop, and the tooth buds themselves. We have also identified the orthologous mouse Tbx22 gene and performed expression analysis in E12.5-E17.5 mouse embryos. The location of mRNA expression closely correlates between mouse and human, while at later stages of development, we also detected expression in mouse lung and whisker follicles. We conclude that expression of TBX22 is entirely consistent with the CPX phenotype and that the mouse should provide a useful model for elucidating its role in craniofacial development.
伴有舌系带过短的腭裂（CPX；MIM 303400）作为一种孟德尔半显性X连锁疾病遗传，已在来自不同种族的几个大家族中被描述。它是一种常见先天性疾病——非综合征性腭裂的有用遗传模型。最近，CPX的潜在遗传缺陷被确定，在含T盒的转录因子TBX22中发现了独特的突变。在此，我们报告两例新的家族性病例，分别出现了新的错义突变和插入突变，均发生在T盒结构域内，突出了这个DNA结合基序的功能重要性。我们描述了TBX22在人类早期发育中的表达情况，其在腭突中表达，在升至舌上方水平位置之前表达最高。在与CPX患者所见舌系带过短相对应的舌系带区域的舌根中也检测到了mRNA。其他表达部位包括与腭突融合的鼻中隔下部、牙胚发育的间充质以及牙胚本身。我们还鉴定了直系同源的小鼠Tbx22基因，并在E12.5 - E17.5小鼠胚胎中进行了表达分析。小鼠和人类之间mRNA表达的位置密切相关，而在发育后期，我们在小鼠肺和触须毛囊中也检测到了表达。我们得出结论，TBX22的表达与CPX表型完全一致，并且小鼠应能为阐明其在颅面发育中的作用提供一个有用的模型。
