Lee Ming Ta Michael, Tsai Anne Chun-Hui, Chou Ching-Heng, Sun Feng-Mei, Huang Li-Chen, Yen Pauline, Lin Chyi-Chyang, Liu Chih-Yang, Wu Jer-Yuarn, Chen Yuan-Tsong, Tsai Fuu-Jen
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan,
Genomic Med. 2008 Jan;2(1-2):45-9. doi: 10.1007/s11568-008-9024-y. Epub 2008 Aug 12.
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.
锁骨颅骨发育不全（CCD；MIM 119600）是一种罕见的常染色体显性疾病，其特征为面部、牙齿和骨骼畸形。迄今为止，涉及RUNX2（位于6p21上，编码成骨细胞分化所需转录因子）的重排和突变是CCD唯一已知的分子病因。然而，仅发现70%的患者存在点突变，13%存在大片段/连续缺失，其余17%仍不清楚。我们确定了一个由八名具有CCD表型的受影响个体组成的家系。直接测序分析未发现RUNX2存在突变。进行了实时定量PCR，结果显示RUNX2存在外显子2至外显子6的基因内缺失。我们的患者不仅展示了作为CCD新机制的独特基因变化，还突出了在进行广泛基因搜寻之前，在疑似家族性病例中考虑“缺失”和“重复”的重要性。
