title: Intragenic microdeletion of RUNX2 is a novel mechanism for cleidocranial dysplasia.
abstract: 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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, mikelee@ibms.sinica.edu.tw.
authors.forename: Ming Ta Michael
authors.initials: MT
authors.lastname: Lee
authors.forename: Anne Chun-Hui
authors.initials: AC
authors.lastname: Tsai
authors.forename: Ching-Heng
authors.initials: CH
authors.lastname: Chou
authors.forename: Feng-Mei
authors.initials: FM
authors.lastname: Sun
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Huang
authors.forename: Pauline
authors.initials: P
authors.lastname: Yen
authors.forename: Chyi-Chyang
authors.initials: CC
authors.lastname: Lin
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Liu
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai