Narin Intarak1, Thunyaporn Budsamongkol1,2, Thanakorn Theerapanon3, Theerapat Chanamuangkon4, Anucharte Srijunbarl5, Lawan Boonprakong6, Thantrira Porntaveetus1, Vorasuk Shotelersuk7,8. 1. Genomics and Precision Dentistry Research Unit, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. 2. Geriatric Dentistry and Special Patients Care Program, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. 3. Excellence Center in Regenerative Dentistry, Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. 4. Biomaterial Testing Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. 5. Dental Materials R&D Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. 6. Oral Biology Research Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. 7. Center of Excellence for Medical Genomics, Medical Genomics Cluster, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 8. Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand.
Abstract
OBJECTIVES: To investigate tooth ultrastructure and mutation of two patients in a family affected with osteogenesis imperfecta (OI) type IV and dentinogenesis imperfecta (DGI). METHODS: Mutations were detected by whole exome and Sanger sequencing. The permanent second molar obtained from the proband (DGI1) and the primary first molar from his affected son (DGI2) were studied for their color, roughness, mineral density, hardness, elastic modulus, mineral content, and ultrastructure, compared to the controls. RESULTS: Two novel missense COL1A2 variants, c.752C > T (p.Ser251Phe) and c.758G > T (p.Gly253Val), were identified in both patients. The c.758G > T was predicted to be the causative mutation. Pulp cavities of DGI1 (permanent teeth) were obliterated while those of DGI2 (primary teeth) were wide. The patients' teeth had darker and redder colors; reduced dentin hardness; decreased, disorganized, and scattered dentinal tubules and collagen fibers; and irregular dentinoenamel junction (DEJ), compared to controls. Lacunae-like structures were present in DGI2. CONCLUSIONS: We reported the novel causative mutation, c.758G > T (p.Gly253Val), in COL1A2 for OI type IV and DGI. The DGI dentin demonstrated inferior mechanical property and ultrastructure, suggesting severe disturbances of dentin formation. These could contribute to fragility and prone to infection of DGI teeth. This study expands phenotypic and genotypic spectra of COL1A2 mutations.
OBJECTIVES: To investigate tooth ultrastructure and mutation of two patients in a family affected with osteogenesis imperfecta (OI) type IV and dentinogenesis imperfecta (DGI). METHODS: Mutations were detected by whole exome and Sanger sequencing. The permanent second molar obtained from the proband (DGI1) and the primary first molar from his affected son (DGI2) were studied for their color, roughness, mineral density, hardness, elastic modulus, mineral content, and ultrastructure, compared to the controls. RESULTS: Two novel missense COL1A2 variants, c.752C > T (p.Ser251Phe) and c.758G > T (p.Gly253Val), were identified in both patients. The c.758G > T was predicted to be the causative mutation. Pulp cavities of DGI1 (permanent teeth) were obliterated while those of DGI2 (primary teeth) were wide. The patients' teeth had darker and redder colors; reduced dentin hardness; decreased, disorganized, and scattered dentinal tubules and collagen fibers; and irregular dentinoenamel junction (DEJ), compared to controls. Lacunae-like structures were present in DGI2. CONCLUSIONS: We reported the novel causative mutation, c.758G > T (p.Gly253Val), in COL1A2 for OI type IV and DGI. The DGI dentin demonstrated inferior mechanical property and ultrastructure, suggesting severe disturbances of dentin formation. These could contribute to fragility and prone to infection of DGI teeth. This study expands phenotypic and genotypic spectra of COL1A2 mutations.
Authors: Qin Du; Li Cao; Yi Liu; Chunyan Pang; Si Wu; Liwei Zheng; Wei Jiang; Xiaoxue Na; Jing Yu; Shasha Wang; Xianjun Zhu; Jiyun Yang Journal: Ann Transl Med Date: 2021-11