Intragenic microdeletion of RUNX2 is a novel mechanism for cleidocranial dysplasia.
Intragenic microdeletion of RUNX2 is a novel mechanism for cleidocranial dysplasia.
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DOI：
10.1007/s11568-008-9024-y
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发表时间：
2008-01-01
期刊：
影响因子：
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通讯作者：
Tsai, Fuu-Jen
中科院分区：
文献类型：
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作者：
Lee, Ming Ta Michael;Tsai, Anne Chun-Hui;Tsai, Fuu-Jen
颅骨锁骨发育不全（CCD；MIM 119600）是一种罕见的常染色体显性遗传病，其特征为面部、牙齿和骨骼畸形。到目前为止，涉及位于6p21编码成骨细胞分化所需转录因子的RUNX2的重排和突变是CCD唯一已知的分子病因。然而，仅发现70%的患者有点突变，13%有大片段/连续缺失，其余17%的病因仍不清楚。我们确定了一个有8名患有CCD表型个体的家族。直接测序分析显示RUNX2无突变。进行实时定量PCR检测到RUNX2存在外显子2到外显子6的基因内缺失。我们的患者不仅展示了一种作为CCD新机制的独特基因改变，而且强调了在进行大量基因探寻工作之前，在疑似家族性病例中考虑“缺失”和“重复”的重要性。
Cleidocranial dysplasia (CCD; MIM 119600) is a rare autosomal dominant disorder characterized by facial, dental, and skeletal malformations. To date, rearrangement and mutations involving RUNX2, which encodes a transcription factor required for osteoblast differentiation on 6p21, has been the only known molecular etiology for CCD. However, only 70% patients were found to have point mutations, 13% large/contiguous deletion but the rest of 17% remains unknown. We ascertained a family consisted of eight affected individuals with CCD phenotypes. Direct sequencing analysis revealed no mutations in the RUNX2. Real time quantitative PCR were performed which revealed an exon 2 to exon 6 intragenic deletion in RUNX2. Our patients not only demonstrated a unique gene change as a novel mechanism for CCD, but also highlight the importance of considering "deletion" and "duplication" in suspected familial cases before extensive effort of gene hunting be carried.