상아질 형성부전증 제 II 형의 원인이 되는 Frameshift 돌연변이
A Frameshift Mutation causes Dentinogenesis Imperfecta Type II
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
상아질 형성부전증 제 II 형은 상아질 기질에 영향을 미치는 유전질환으로 dentin sialophosphoprotien(DSPP )의 돌연변이에 기인한다. DSPP 발현 산물 중 하나인 dentin phosphoprotein(DPP)은 Asp-Ser-Ser 서열이 반복되는 독특한 구조로, 상아질 석회화 성숙 과정에 관여한다. 본 연구는 DPP 영역을 포함한 DSPP 유전자 염기 서열 분석을 통하여 유전성 상아질 결함의 원인이 되는 돌연변이를 확인하고자 하였다. 임상적 및 방사선학적 검사와 DSPP 유전자 염기 서열 분석 및 DPP 영역의 allele-specific cloning을 시행하여 비교 분석한 결과, 2688번 염기인 티민의 결실(c.2688delT)이 확인 되었고, -1 bp frameshift 돌연변이를 야기하였다. 이는 친수성 아미노산을 소수성으로치환시켜, DPP 특성의 변화 및 상호작용 능력 저하를 일으켜 상아질 형성부전증 제 II 형의 원인으로 작용하였다.
Abstract
Dentinogenesis imperfecta type II (DGI-II) is an inherited disorder affecting the dentin matrix and is related to mutations in the dentin sialophosphoprotein (DSPP ) gene. The protein encoded by the DSPP gene undergoes extensive posttranslational modifications. Dentin phosphoprotein (DPP), one of the DSPP expressed products, has unique composition with highly repetitive Asp-Ser-Ser amino acid residues and is related to the maturation of dentin mineralization. We aimed to identify mutation in DSPP , including the DPP coding region, contributing to inherited dentin defects in a Korean family with DGI-II. Clinical and radiographic examinations were performed, and all five exons and exon-intron boundaries of the DSPP gene were sequenced. Additionally, allele-specific cloning for highly repetitive DPP region was performed. By sequencing and cloning, a heterozygous single nucleotide deletion (c.2688delT) was identified. The identified mutation caused a frameshift in the DPP coding region. This frameshift mutation would introduce hydrophobic amino acids instead of hydrophilic amino acids and would result in a change in the characteristics of DPP.
참고문헌 (14)
- Kim JW, "Hereditary dentin defects", J Dent Res, 86, pp.392~399 (2007)
- Shields ED, "A proposed classification for heritable human dentine defects with a description of a new entity", Arch Oral Biol, 18, pp.543~553 (1973)
- Kim JW, "A novel splice acceptor mutation in the DSPP gene causing dentinogenesis imperfecta type II", Hum Genet, 115, pp.248~254 (2004)
- Lee KE, "Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II", Clin Genet, 79, pp.378~384 (2011)
- Nieminen P, "Frameshift mutations in dentin phosphoprotein and dependence of dentin disease phenotype on mutation location", J Bone Miner Res, 26, pp.873~880 (2011)
- MacDougall M, "Dentin phosphoprotein and dentin sialoprotein are cleavage products expressed from a single transcript coded by a gene on human chromosome 4. Dentin phosphoprotein DNA sequence determination", J Biol Chem, 272, pp.835~842 (1997)
- Wang SK, "Enamel malformations associated with a defined dentin sialophosphoprotein mutation in two families", Eur J Oral Sci, 119, pp.158~167 (2011)
- Song YL, "Dentin phosphoprotein frameshift mutations in hereditary dentin disorders and their variation patterns in normal human population", J Med Genet, 45, pp.457~464 (2008)
- Lee SK, "A novel mutation in the DSPP gene associated with dentinogenesis imperfecta type II", J Dent Res, 88, pp.51~55 (2009)
- McKnight DA, "Overlapping DSPP mutations cause dentin dysplasia and dentinogenesis imperfecta", J Dent Res, 87, pp.1108~1111 (2008)
- Bloch-Zupan A, "Detection of a Novel DSPP Mutation by NGS in a Population Isolate in Madagascar", Front physiol, 7, pp.70~ (2016)
- McKnight DA, "A comprehensive analysis of normal variation and disease-causing mutations in the human DSPP gene", Hum mutat, 29, pp.1392~1404 (2008)
- George A, "The carboxylterminal domain of phosphophoryn contains unique extended triplet amino acid repeat sequences forming ordered carboxyl-phosphate interaction ridges that may be essential in the biomineralization process", J Biol Chem, 271, pp.32869~32873 (1996)
- Suzuki S, "Dentin sialoprotein and dentin phosphoprotein have distinct roles in dentin mineralization", Matrix Biol, 28, pp.221~229 (2009)