Identification of a new mutation in the CBFA1 Runt Domain of a patient with cleidocranial dysplasia

TSUJIGIWA H, NAGATSUKA H, GUNDUZ M, TAMAMURA R, RODRIGUEZ AP, HAN PP, INOUE M, SETSU K, YAMACHIKA E, SUGAHARA T, NAGAI N

Taipei (Taiwán)

Simposio; TMU International Symposium on Life Science Current Progress in Human Life Science; 2002

Taipei Medical University

Background and aim: Cleidocranial dysplasia (CCD) is an autosomal dominant and hereditary skeletal disorder. Mutated Cbfal locus in mice showed specific skeletal abnormalities that are characteristics of the human CCD. The patients with CCD had various deletions at chromosomal area 6p21, which is the location for CBFAl gene. Later, mutations of this gene were detected in patients with CCD, making it clear that CBFAl was the gene responsible for human CCD. CBFAl is a transcription factor that belongsyo the gene family with runt-domain. It has a DNA binding domain, runt, which is homologous with drosophila pair-rule gene runt. We examined a patient with CCD and cleft lip and found a new mutation in CBFAl gene. The clinical and radiological examination reyealed a prolonged retention of deciduos teeth, aplasia of the clavicles, and cleft lip. Methods: DNA was extracted from fresh whole blood and used as a template for PCR. Amplification of each exon and sequencing was performed. Results: A mutation was detected in exon 3 of CBFAl gene. A heterozygous CAA to TAA nucleotide change at codon 195 caused an aminoacid substitution from glutamin to stop codon in the runt domain of CBFAl gene. This is a new mutation of CBFAl gene in patients with CCD. Conclusions: As many types of CBFAl mutations have been reported, there may be additional mutations that have not been detected. It is possible that some types of mutant CBFAl damage the process of odontoblast or fibroblast differentiation. Further studies are required for elucidation of these phenomena