Journal of the korean academy of Pediatric Dentistry (대한소아치과학회지)

Korean Academy of Pediatric Dentistry (대한소아치과학회)
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A Novel RUNX2 Mutation in a Korean Family with Cleidocranial Dysplasia

한국인 쇄골 두개 이형성증 가족에서의 RUNX2 유전자 돌연변이

  • Lee, Ji Won (Department of Pediatric Dentistry, School of Dentistry, Seoul National University) ;
  • Song, Jisoo (Department of Pediatric Dentistry, School of Dentistry, Seoul National University) ;
  • Shin, Teo Jeon (Department of Pediatric Dentistry, School of Dentistry, Seoul National University) ;
  • Hyun, Hong-Keun (Department of Pediatric Dentistry, School of Dentistry, Seoul National University) ;
  • Kim, Young-Jae (Department of Pediatric Dentistry, School of Dentistry, Seoul National University) ;
  • Lee, Sang-Hoon (Department of Pediatric Dentistry, School of Dentistry, Seoul National University) ;
  • Kim, Jongbin (Department of Pediatric Dentistry, College of Dentistry, Dankook University) ;
  • Kim, Jung-Wook (Department of Pediatric Dentistry, School of Dentistry, Seoul National University)
  • 이지원 (서울대학교 치의학대학원 소아치과학교실) ;
  • 송지수 (서울대학교 치의학대학원 소아치과학교실) ;
  • 신터전 (서울대학교 치의학대학원 소아치과학교실) ;
  • 현홍근 (서울대학교 치의학대학원 소아치과학교실) ;
  • 김영재 (서울대학교 치의학대학원 소아치과학교실) ;
  • 이상훈 (서울대학교 치의학대학원 소아치과학교실) ;
  • 김종빈 (단국대학교 치과대학 소아치과학교실) ;
  • 김정욱 (서울대학교 치의학대학원 소아치과학교실)
  • Received : 2019.08.16
  • Accepted : 2019.09.19
  • Published : 2019.11.30
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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.

쇄골 두개 이형성증(Cleidocranial dysplasia)은 상염색체 우성의 유전질환으로, 두개골 간 봉합 지연, 쇄골의 이형성, 과잉치, 영구치 맹출 지연 등을 특징으로 한다. 경조직 형성 조절 인자인 Runt-related transcription factor 2 (RUNX2)의 돌연변이가 쇄골 두개 이형성증을 유발하는 주요 요인으로 보고되고 있다. 이 연구는 치아 맹출 지연이 관찰되는 쇄골 두개 이형성증 가계에서 분자유전학적 원인을 규명하고자 하였다. 23세 여성 환자와 그 어머니를 대상으로 임상 검사 및 방사선 검사를 진행하였고 RUNX2 유전자의 염기 서열을 분석하였다. 대상자 모두에서 3번 exon 내의 단일 염기 결손 돌연변이(NM_001024630.4: c.357delC)를 확인하였다. 이로 인해 frameshift가 발생하여 조기 종결 코돈이 형성될 것으로 예측되며[p.(Asn120Thrfs*24)], 이로 인한 RUNX2 단백질의 기능 손상이 해당 가계에서 나타난 영구치 맹출 지연의 병인이 되었을 것으로 여겨진다.

Keywords

References

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