一种预测会破坏DNA结合的新型RUNX2错义突变，在一个伴有指甲增生的中国大家庭中导致了锁骨颅骨发育不全。
A novel RUNX2 missense mutation predicted to disrupt DNA binding causes cleidocranial dysplasia in a large Chinese family with hyperplastic nails.
作者信息
Tang Shaohua, Xu Qiyu, Xu Xueqin, Du Jicheng, Yang Xuemei, Jiang Yusheng, Wang Xiaoqin, Speck Nancy, Huang Taosheng
机构信息
The prenatal diagnostic Center of Wenzhou City, Department of genetics of Wenzhou No2 Hospital, Wenzhou, China.
出版信息
BMC Med Genet. 2007 Dec 31;8:82. doi: 10.1186/1471-2350-8-82.
BACKGROUND
Cleidocranial dysplasia (CCD) is a dominantly inherited disease characterized by hypoplastic or absent clavicles, large fontanels, dental dysplasia, and delayed skeletal development. The purpose of this study is to investigate the genetic basis of Chinese family with CCD.
METHODS
Here, a large Chinese family with CCD and hyperplastic nails was recruited. The clinical features displayed a significant intrafamilial variation. We sequenced the coding region of the RUNX2 gene for the mutation and phenotype analysis.
RESULTS
The family carries a c.T407C (p.L136P) mutation in the DNA- and CBFbeta-binding Runt domain of RUNX2. Based on the crystal structure, we predict this novel missense mutation is likely to disrupt DNA binding by RUNX2, and at least locally affect the Runt domain structure.
CONCLUSION
A novel missense mutation was identified in a large Chinese family with CCD with hyperplastic nails. This report further extends the mutation spectrum and clinical features of CCD. The identification of this mutation will facilitate prenatal diagnosis and preimplantation genetic diagnosis.
背景
锁骨颅骨发育不全（CCD）是一种常染色体显性遗传病，其特征为锁骨发育不全或缺失、囟门大、牙齿发育异常以及骨骼发育迟缓。本研究旨在探究一个患有CCD的中国家系的遗传基础。
方法
在此，我们招募了一个患有CCD且指甲增生的中国大家系。临床特征显示出显著的家系内变异。我们对RUNX2基因的编码区进行测序以进行突变和表型分析。
结果
该家系在RUNX2基因的DNA和CBFβ结合Runt结构域中携带一个c.T407C（p.L136P）突变。基于晶体结构，我们预测这个新的错义突变可能会破坏RUNX2与DNA的结合，并至少局部影响Runt结构域的结构。
结论
在一个患有CCD且指甲增生的中国大家系中鉴定出一个新的错义突变。本报告进一步扩展了CCD的突变谱和临床特征。该突变的鉴定将有助于产前诊断和植入前基因诊断。
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