Background: Cleidocranial dysplasia (CCD) is an autosomal-dominant skeletal dysplasia syndrome characterized by delayed closure of cranial sutures, remained-open fontanels, hypoplastic clavicles, abnormal dentition including retention of the primary teeth and delayed eruption of secondary dentition, and short stature. The responsible gene for CCD is RUNX2, which encodes an important transcription factor for osteoblast development and bone formation. CCD is caused by the haploinsufficiency of RUNX2.
Objective: To analyze the clinical manifestations and the mutation of RUNX2 gene in two CCD patients.
Methods: Clinical data and peripheral venous blood samples were collected from two patients. Genomic DNA was extracted from peripheral blood samples, Polymerase Chain Reaction(PCR) and Sanger sequencing were performed to analyze the possible mutation of RUNX2 gene.
Results: The two patients appear with typical CCD phenotypes involving clavicular hypoplasia, patent fontanels, dental abnormalities and short stature. Sanger sequencing revealed two novel heterozygous mutations of RUNX2 gene in two patients. One nonsense mutation c.1123C>T (Q375X) in patient 1, another is a frameshift mutation 1126delT (F376S) in patient 2, both cause a premature termination of translation and an truncated protein of RUNX2.
Conclusion: RUNX2 is the pathogenic gene for CCD. Here we identified two unreported mutations of RUNX2 gene in two CCD patients, which elucidated the molecular mechanism for their CCD phenotypes and further enrich the mutation spectrum of RUNX2 gene.
14 May 2016 - 17 May 2016