Data from: Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents with osteogenesis imperfecta - a retrospective cohort study

Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, caused mainly by mutations in the collagen I genes (COL1A1 and COL1A2). Dentinogenesis imperfecta (DGI) and other dental aberrations are common features of OI. We investigated the association between collagen I mutations and DGI, taurodontism, and retention of permanent second molars in a retrospective cohort of 152 unrelated children and adolescents with OI. The clinical examination included radiographic evaluations. Teeth from 81 individuals were available for histopathological evaluation. COL1A1/2 mutations were found in 104 individuals by nucleotide sequencing. DGI was diagnosed clinically and radiographically in 29% of the individuals (44/152) and through isolated histological findings in another 19% (29/152). In the individuals with a COL1A1 mutation, 70% (7/10) of those with a glycine substitution located C-terminal of p.Gly305 exhibited DGI in both dentitions while no individual (0/7) with a mutation N-terminal of this point exhibited DGI in either dentition (p = 0.01). In the individuals with a COL1A2 mutation, 80% (8/10) of those with a glycine substitution located C terminal of p.Gly211 exhibited DGI in both dentitions while no individual (0/5) with a mutation N-terminal of this point (p = 0.007) exhibited DGI in either dentition. DGI was restricted to the deciduous dentition in 20 individuals. Seventeen had missense mutations where glycine to serine was the most prevalent substitution (53%). Taurodontism occurred in 18% and retention of permanent second molars in 31% of the adolescents. Dental aberrations are strongly associated with qualitatively changed collagen I. The varying expressivity of DGI is related to the location of the collagen I mutation. Genotype information may be helpful in identifying individuals with OI who have an increased risk of dental aberrations.

成骨不全症（Osteogenesis imperfecta, OI）是一类异质性结缔组织疾病，主要由I型胶原基因（COL1A1与COL1A2）的突变所致。牙本质发育不全（Dentinogenesis imperfecta, DGI）及其他牙齿异常是成骨不全症的常见临床表现。本研究针对152名无亲缘关系的成骨不全症儿童及青少年开展回顾性队列研究，旨在探讨I型胶原突变与牙本质发育不全、牛牙症（taurodontism）以及恒牙第二磨牙滞留之间的相关性。临床检查涵盖影像学评估。其中81名受试者的牙齿样本可供组织病理学分析。通过核苷酸测序，我们在104名受试者中检测到COL1A1/2突变。29%（44/152）的受试者经临床与影像学检查确诊为牙本质发育不全，另有19%（29/152）的受试者仅通过独立的组织病理学结果确诊。在携带COL1A1突变的受试者中，70%（7/10）的p.Gly305位点C端存在甘氨酸替换的受试者，上下颌牙列均出现牙本质发育不全；而该位点N端存在突变的受试者中，无一人（0/7）任何牙列出现牙本质发育不全（p=0.01）。在携带COL1A2突变的受试者中，80%（8/10）的p.Gly211位点C端存在甘氨酸替换的受试者，上下颌牙列均出现牙本质发育不全；而该位点N端存在突变的受试者中，无一人（0/5）任何牙列出现牙本质发育不全（p=0.007）。另有20名受试者的牙本质发育不全仅累及乳牙列。其中17名受试者携带错义突变，最常见的替换类型为甘氨酸突变为丝氨酸（占比53%）。在青少年受试者中，牛牙症的发生率为18%，恒牙第二磨牙滞留的发生率为31%。牙齿异常与结构异常的I型胶原显著相关。牙本质发育不全的表型差异与I型胶原突变的位点密切相关。基因型信息或可辅助识别存在牙齿异常高风险的成骨不全症患者。