Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents with osteogenesis imperfecta - A retrospective cohort study.
Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents with osteogenesis imperfecta - A retrospective cohort study.
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DOI：
10.1371/journal.pone.0176466
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Malmgren B
中科院分区：
文献类型：
--
作者：
Andersson K;Dahllöf G;Lindahl K;Kindmark A;Grigelioniene G;Åström E;Malmgren B
成骨不全症（Osteogenesis imperfecta， OI）是一种异质性结缔组织疾病，主要由胶原I基因（COL1A1和COL1A2）突变引起。牙本质发育不全（DGI）和其他牙齿畸变是成骨不全的常见特征。我们对152名无血缘关系的成骨不全症儿童和青少年进行了回顾性研究，研究了I型胶原突变与DGI、牛牙畸形和恒磨牙保留之间的关系。临床检查包括影像学评价。81个个体的牙齿可用于组织病理学评估。通过核苷酸测序，在104例个体中发现COL1A1/2突变。29%的个体（44/152）通过临床和影像学诊断为DGI，另有19%（29/152）通过单独的组织学发现诊断为DGI。在COL1A1突变个体中，70%（7/10）在p. gly305的c端有甘氨酸取代的个体在两个牙列中都表现出DGI，而在这个点的n端有突变的个体（0/7）在两个牙列中都没有表现出DGI （p = 0.01）。在COL1A2突变个体中，80%（8/10）位于p. gly211的C端甘氨酸取代的个体在两个牙列中都表现出DGI，而没有个体（0/5）在这个点的n端突变（p = 0.007）在两个牙列中都表现出DGI。DGI局限于20个个体的乳牙列。17例有错义突变，其中甘氨酸为丝氨酸是最常见的替换（53%）。18%的青少年出现了牛牙症，31%的青少年有恒磨牙保留。牙齿畸变与I型胶原质的改变密切相关，DGI表达的不同与I型胶原突变的位置有关。基因型信息可能有助于识别有牙齿畸变风险增加的成骨不全患者。
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.