Intragenic microdeletion of RUNX2 is a novel mechanism for cleidocranial dysplasia
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. © 2008 Springer Science+Business Media B.V.
Lee, MTM; Tsai, ACH; Chou, CH; Sun, FM; Huang, LC; Yen, P; Lin, CC; Liu, CY; Wu, JY; Chen, YT; Tsai, FJ
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