RUNX2 mutations in cleidocranial dysplasia patients.
OBJECTIVE
Mutations in the RUNX2 gene, a master regulator of bone formation, have been identified in cleidocranial dysplasia (CCD) patients. CCD is a rare autosomal-dominant disease characterized by the delayed closure of cranial sutures, defects in clavicle formation, and supernumerary teeth. The purposes of this study were to identify genetic causes of two CCD nuclear families and to report their clinical phenotypes.


METHODS
We identified two CCD nuclear families and performed mutational analyses to clarify the underlying molecular genetic etiology.


RESULTS
Mutational analysis revealed a novel nonsense mutation (c.273T>A, p.L93X) in family 1 and a de novo missense one (c.673C>T, p.R225W) in family 2. Individuals with a nonsense mutation showed maxillary hypoplasia, delayed eruption, multiple supernumerary teeth, and normal stature. In contrast, an individual with a de novo missense mutation in the Runt domain showed only one supernumerary tooth and short stature.


CONCLUSIONS
Mutational and phenotypic analyses showed that the severity of mutations on the skeletal system may not necessarily correlate with that of the disruption of tooth development.
Ryoo
H-M
HM
Department of Cell and Developmental Biology, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, Seoul 110-768, Korea.
Kang
H-Y
HY
Lee
S-K
SK
Lee
K-E
KE
Kim
J-W
JW
D002648:Child; D002973:Cleidocranial Dysplasia / Q000150:complications / Q000235:genetics*; D018389:Codon, Nonsense; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D014096:Tooth, Supernumerary / Q000209:etiology
D018389:Codon, Nonsense; D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human