A Novel RUNX2 Mutation in a Korean Family with Cleidocranial Dysplasia (한국인 쇄골 두개 이형성증 가족에서의 RUNX2 유전자 돌연변이)

Ji Won Lee (이지원); Ji-Soo Song (송지수); Teo Jeon Shin (신터전); Hong-Keun Hyun (현홍근); Young Jae Kim (김영재); Sang-Hoon Lee (이상훈); Jongbin Kim (김종빈); Jung-Wook Kim (김정욱)

doi:10.5933/JKAPD.2019.46.4.409

A Novel RUNX2 Mutation in a Korean Family with Cleidocranial Dysplasia

Journal of the Korean academy of pediatric dentistry
Abbr : J Korean Acad Pediatr Dent
2019, 46(4), pp.409~415
DOI : 10.5933/JKAPD.2019.46.4.409
Publisher : The Korean Academy Of Pediatric Dentistry
Research Area : Medicine and Pharmacy > Dentistry
Received : August 16, 2019
Accepted : September 19, 2019
Published : November 27, 2019

Ji Won Lee ¹, Ji-Soo Song ², Teo Jeon Shin ³, Hong-Keun Hyun ³, Young Jae Kim ³, Sang-Hoon Lee ³, Jongbin Kim ⁴, Jung-Wook Kim ³

¹서울대학교치과병원
²서울대학교 치의학대학원 소아치과학교실
³서울대학교
⁴단국대학교

Accredited

ABSTRACT

Cleidocranial dysplasia (CCD) is an autosomal-dominant disease characterized by the delayed closure of cranial sutures, defects in clavicle formation, supernumerary teeth, and delayed tooth eruption. Defects in the Runt-related transcription factor 2 (RUNX2 ), a master regulator of bone formation, have been identified in CCD patients. The aim of this study was to identify the molecular genetic causes in a CCD family with delayed tooth eruption. The 23-year-old female proband and her mother underwent clinical and radiographic examinations, and all coding exons of the RUNX2 were sequenced. Mutational analysis revealed a single nucleotide deletion mutation (NM_001024630.4 : c.357delC) in exon 3 in the proband and her mother. The single C deletion would result in a frameshift in translation and introduce a premature stop codon [p.(Asn120Thrfs*24)]. This would result in the impaired function of RUNX2 protein, which may be the cause of delayed eruption of permanent teeth in the family.

KEYWORDS

RUNX2, Cleidocranial dysplasia, Deletion mutation, Frameshift, Delayed eruption

Journal Copyright Policy

This license enables reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.

Citation status

* References for papers published after 2025 are currently being built.

[journal] Mundlos S / 1999 / Cleidocranial dysplasia : clinical and molecular genetics / J Med Genet 36 : 177~182

[journal] Mundlos S / 1997 / Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia / Cell 89 : 773~779

[web] GeneReviews / Cleidocranial Dysplasia Spectrum Disorder / https://www.ncbi.nlm.nih.gov/books/NBK1513/

[journal] Ogawa E / 1993 / PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene / Proc Natl Acad Sci U S A 90 : 6859~6863

[journal] Ducy P / 1995 / Two distinct osteoblast-specific cis acting elements control expression of a mouse osteocalcin gene / Mol Cell Biol 15 : 1858~1869

[journal] Ducy P / 1997 / Osf2/Cbfa1 : a transcriptional activator of osteoblast differentiation / Cell 89 : 747~754

[journal] Jiménez MJ / 1999 / Collagenase 3 is a target of Cbfa1, a transcription factor of the runt gene family involved in bone formation / Mol Cellular Biol 19 : 4431~4442

[journal] Dhamija S / 2001 / Role of Cbfa1 in ameloblastin gene transcription / J Biol Chem 276 : 35159~35164

[journal] Zheng Q / 2003 / Type X collagen gene regulation by Runx2 contributes directly to its hypertrophic chondrocyte-specific expression in vivo / J Cell Biol 162 : 833~842

[journal] Jaruga, A / 2016 / Cleidocranial dysplasia and RUNX2-clinical phenotypegenotype correlation / Clin Genet 90 : 393~402

[journal] Heinrich J / 2005 / CSF-1, RANKL and OPG regulate osteoclastogenesis during murine tooth eruption / Arch Oral Biol 50 : 897~908

[journal] Thirunavukkarasu K / 2000 / The osteoblast-specific transcription factor Cbfa1 contributes to the expression of osteoprotegerin, a potent inhibitor of osteoclast differentiation and function / J Biol Chem 275 : 25163~25172

[journal] Kitazawa R / 1999 / Promoter structure of mouse RANKL/TRANCE/OPGL/ODF gene / Biochim Biophys Acta 1445 : 134~141

[journal] Dorotheou D / 2013 / Tooth eruption : altered gene expression in the dental follicle of patients with cleidocranial dysplasia / Orthod Craniofac Res 16 : 20~27

[journal] Yoda S / 2004 / Delayed tooth eruption and suppressed osteoclast number in the eruption pathway of heterozygous Runx2/Cbfa1 knockout mice / Arch Oral Biol 49 : 435~442

[journal] Camilleri S / 2006 / Runx2 and dental development / Eur J Oral Sci 114 : 361~373

[journal] Ishii K / 1998 / Characteristics of jaw growth in cleidocranial dysplasia / Cleft Palate Craniofac J 35 : 161~166

[journal] Jensen BL / 1990 / Development of the dentition in cleidocranial dysplasia / J Oral Pathol Med 19 : 89~93

[journal] Wang XP / 2005 / Runx2(Cbfa1)inhibits Shh signaling in the lower but not upper molars of mouse embryos and prevents the budding of putative successional teeth / J Dent Res 84 : 138~143

[journal] Cobourne MT / 2001 / Sonic hedgehog regulates epithelial proliferation and cell survival in the developing tooth germ / J Dent Res 80 : 1974~1979

[journal] Lukinmaa PL / 1995 / Histological observations of teeth and peridental tissues in cleidocranial dysplasia imply increased activity of odontogenic epithelium and abnormal bone remodeling / J Craniofac Genet Dev Biol 15 : 212~221

[journal] Jensen BL / 1992 / Dental treatment strategies in cleidocranial dysplasia / Br Dent J 172 : 243~247

[journal] Lou Y / 2009 / A Runx2 threshold for the cleidocranial dysplasia phenotype / Hum Mol Genet 18 : 556~568

[journal] Zhou, G / 1999 / CBFA1 mutation analysis and functional correlation with phenotypic variability in cleidocranial dysplasia / Hum Mol Genet 8 : 2311~2316

KJCKorea
Journal Central

Journal of the Korean academy of pediatric dentistry 2025 KCI Impact Factor : 0.43

A Novel RUNX2 Mutation in a Korean Family with Cleidocranial Dysplasia

ABSTRACT

KEYWORDS

Journal Copyright Policy

Citation status

* References for papers published after 2025 are currently being built.

Journal of the Korean academy of pediatric dentistry 2025 KCI Impact Factor : 0.43

A Novel RUNX2 Mutation in a Korean Family with Cleidocranial Dysplasia

ABSTRACT

KEYWORDS

Journal Copyright Policy

Statistics

Tools

Issue List

Citation status

KCI Citation Counts (1)

REFERENCES (24) * References for papers published after 2025 are currently being built.

Search PDF

Citation

* References for papers published after 2025 are currently being built.