A novel RUNX2 missense mutation predicted to disrupt DNA binding causes cleidocranial dysplasia in a large Chinese family with hyperplastic nails
1 The prenatal diagnostic Center of Wenzhou City, Department of genetics of Wenzhou No2 Hospital, Wenzhou, China
2 Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire, USA
3 Department of Pediatrics, Division of Human Genetics & Metabolism, Department of Developmental and Cell Biology, Department of Pathology, University of California, Irvine, CA, USA
BMC Medical Genetics 2007, 8:82 doi:10.1186/1471-2350-8-82Published: 31 December 2007
Cleidocranial dysplasia (CCD) is a dominantly inherited disease characterized by hypoplastic or absent clavicles, large fontanels, dental dysplasia, and delayed skeletal development. The purpose of this study is to investigate the genetic basis of Chinese family with CCD.
Here, a large Chinese family with CCD and hyperplastic nails was recruited. The clinical features displayed a significant intrafamilial variation. We sequenced the coding region of the RUNX2 gene for the mutation and phenotype analysis.
The family carries a c.T407C (p.L136P) mutation in the DNA- and CBFβ-binding Runt domain of RUNX2. Based on the crystal structure, we predict this novel missense mutation is likely to disrupt DNA binding by RUNX2, and at least locally affect the Runt domain structure.
A novel missense mutation was identified in a large Chinese family with CCD with hyperplastic nails. This report further extends the mutation spectrum and clinical features of CCD. The identification of this mutation will facilitate prenatal diagnosis and preimplantation genetic diagnosis.