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.
Lee
Ming Ta Michael
MT
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, mikelee@ibms.sinica.edu.tw.
Tsai
Anne Chun-Hui
AC
Chou
Ching-Heng
CH
Sun
Feng-Mei
FM
Huang
Li-Chen
LC
Yen
Pauline
P
Lin
Chyi-Chyang
CC
Liu
Chih-Yang
CY
Wu
Jer-Yuarn
JY
Chen
Yuan-Tsong
YT
Tsai
Fuu-Jen
FJ