Correlation between genotype and supernumerary tooth formation in cleidocranial dysplasia.
BACKGROUND
Cleidocranial dysplasia (CCD, MIM#119600), for which the responsible gene is RUNX2, is a genetic disorder characterized by hypoplasia or aplasia of the clavicles, patent fontanelles, and a short stature. Supernumerary teeth and delayed eruption and impaction of permanent teeth are frequently associated with CCD. Our previous study reported wide intrafamilial variation in supernumerary tooth formation associated with a mutation in the RUNT-domain of RUNX2, suggesting a low correlation between the genotype and supernumerary tooth formation. To further clarify this point, a more precise evaluation was performed.


METHODS
Gene mutational analysis of nine Japanese individuals with CCD was performed. Dental and skeletal characteristics were examined based on patient examinations and radiographs.


RESULTS
Four different gene mutations, including one novel mutation in RUNX2 gene (NM_001024630), were identified. Among them, four individuals had the R225Q mutation, three siblings had the P224S mutation, and the other two individuals had different frame-shift mutations. Wide variations in supernumerary tooth formation were observed in individuals with identical gene mutations, and discordance was seen between monozygotic twins. Asymmetric supernumerary tooth formation was noted in five out of the nine individuals.


CONCLUSIONS
Individuals with identical gene mutations showed a wide variation in the supernumerary tooth formation. Not only the genotype but also environmental factors and a complex system including epigenetics and copy number variation might regulate supernumerary tooth formation in CCD.
Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. n-suda.mort@tmd.ac.jp
N
N
Suda
M
M
Hattori
K
K
Kosaki
A
A
Banshodani
K
K
Kozai
K
K
Tanimoto
K
K
Moriyama
D000225:Adenine; D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000235:genetics; D002648:Child; D002973:Cleidocranial Dysplasia / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D018740:Genetic Heterogeneity; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D005973:Glutamine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D011392:Proline / Q000235:genetics; D012694:Serine / Q000235:genetics; D013941:Thymine; D014096:Tooth, Supernumerary / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics
D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D005973:Glutamine; D012694:Serine; D001120:Arginine; D011392:Proline; D000225:Adenine; D013941:Thymine