[Clinical and image features, and identification of pathogenic gene mutation of two cleidocranial dysplasia families].

Objective: Cleidocranial dysplasia (CCD) is a dominantly inherited skeletal dysplasia caused by mutations in the osteoblast-specific transcription factor-encoding gene, core binding factor α1 (CBFA1). Over 90 mutations in CBFA1 gene have been published to date in 500 independent cases of CCD, including missense mutations, deletions, insertions, frameshift, and splice mutations. However, mutational screening of the CBFA1 gene is still far from saturation, and more novel mutations will be identified to enrich the insights into the molecular basis for the pathogenesis of CCD. The aim of this study was to explore the clinical and image features and detect the mutations of CBFA1 gene in two CCD families.

Method: In this study, the clinical features were investigated in two CCD families, radiological and CT examinations regarding osseous malformation were carried out over the entire body of these patients with CCD. Blood (2 ml) was drawn from all affected individuals, unaffected family members and one hundred unrelated normal controls, Genomic DNA was extracted from whole blood with PureGene DNA extraction kit and PCR was performed with eight pairs of PCR primers for exons 0 to 7 of the CBFA1 gene. The mutations of CBFA1 gene were screened in these two CCD families.

Result: (1) The clinical features of patients with CCD include delayed closure of fontanelles, frontal bossing, dysplasia of clavicles, late tooth eruption, and other skeletal anomalies. X-ray and CT examination showed the bulging calvarium, patent fontanelles, wide cranial sutures, multiple Wormian bones, dental dysplasia or aplasia of clavicles. (2) Two mutations were identified, one is novel missense mutation (c.1259C > T[p.T420I]) in CBFA1 gene exon 7, other (c.577C > T[p.R193X]) was reported in Chinese cases with CCD for the first time.

Conclusion: (1) The clinical and image features of patients in two CCD families include delayed closure of fontanelles, frontal bossing, dysplasia of clavicles, late tooth eruption, and other skeletal anomalies. (2) The T420I and R193X mutations of CBFA1 were reported, expanding the spectrum of CBFA1 mutations causing CCD.