한국인 쇄골 두개 이형성증 가족에서의 RUNX2 유전자 돌연변이
A Novel RUNX2 Mutation in a Korean Family with Cleidocranial Dysplasia
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초록
쇄골 두개 이형성증(Cleidocranial dysplasia)은 상염색체 우성의 유전질환으로, 두개골 간 봉합 지연, 쇄골의 이형성, 과잉치, 영구치맹출 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. 대상자모두에서 3번 exon 내의 단일 염기 결손 돌연변이(NM_001024630.4: c.357delC)를 확인하였다. 이로 인해 frameshift가 발생하여 조기종결 코돈이 형성될 것으로 예측되며[p.(Asn120Thrfs*24)], 이로 인한 RUNX2 단백질의 기능 손상이 해당 가계에서 나타난 영구치 맹출지연의 병인이 되었을 것으로 여겨진다.
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.
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