Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta
Abstract Background Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by an increased tendency for fractures throughout life. Autosomal dominant (AD) mutations in COL1A1 and COL1A2 are causative in approximately 85% of cases. In recent years, recessive variants...
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | http://link.springer.com/article/10.1186/s13023-020-01361-4 |
| _version_ | 1811331610433290240 |
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| author | Kristofer Andersson Barbro Malmgren Eva Åström Ann Nordgren Fulya Taylan Göran Dahllöf |
| author_facet | Kristofer Andersson Barbro Malmgren Eva Åström Ann Nordgren Fulya Taylan Göran Dahllöf |
| author_sort | Kristofer Andersson |
| collection | DOAJ |
| description | Abstract Background Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by an increased tendency for fractures throughout life. Autosomal dominant (AD) mutations in COL1A1 and COL1A2 are causative in approximately 85% of cases. In recent years, recessive variants in genes involved in collagen processing have been found. Hypodontia (< 6 missing permanent teeth) and oligodontia (≥ 6 missing permanent teeth) have previously been reported in individuals with OI. The aim of the present cross-sectional study was to investigate whether children and adolescents with OI and oligodontia and hypodontia also present with variants in other genes with potential effects on tooth development. The cohort comprised 10 individuals (7.7–19.9 years of age) with known COL1A1/A2 variants who we clinically and radiographically examined and further genetically evaluated by whole-genome sequencing. All study participants were treated at the Astrid Lindgren Children’s Hospital at Karolinska University Hospital, Stockholm (Sweden’s national multidisciplinary pediatric OI team). We evaluated a panel of genes that were associated with nonsyndromic and syndromic hypodontia or oligodontia as well as that had been found to be involved in tooth development in animal models. Results We detected a homozygous nonsense variant in CREB3L1, p.Tyr428*, c.1284C > A in one boy previously diagnosed with OI type III. COL1A1 and COL1A2 were the only two genes among 9 individuals which carried a pathogenic mutation. We found rare variants with unknown significance in several other genes related to tooth development. Conclusions Our findings suggest that mutations in COL1A1, COL1A2, and CREB3L1 may cause hypodontia and oligodontia in OI. The findings cannot exclude additive effects from other modifying or interacting genes that may contribute to the severity of the expressed phenotype. Larger cohorts and further functional studies are needed. |
| first_indexed | 2024-04-13T16:22:16Z |
| format | Article |
| id | doaj.art-b3f74a87cb05479faea9c91fdaf690bc |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-13T16:22:16Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-b3f74a87cb05479faea9c91fdaf690bc2022-12-22T02:39:51ZengBMCOrphanet Journal of Rare Diseases1750-11722020-03-0115111210.1186/s13023-020-01361-4Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfectaKristofer Andersson0Barbro Malmgren1Eva Åström2Ann Nordgren3Fulya Taylan4Göran Dahllöf5Department of Dental Medicine, Division of Orthodontics and Pediatric Dentistry, Karolinska InstitutetDepartment of Dental Medicine, Division of Orthodontics and Pediatric Dentistry, Karolinska InstitutetDepartment of Women’s and Children’s Health, Karolinska InstitutetDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska InstitutetDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska InstitutetDepartment of Dental Medicine, Division of Orthodontics and Pediatric Dentistry, Karolinska InstitutetAbstract Background Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by an increased tendency for fractures throughout life. Autosomal dominant (AD) mutations in COL1A1 and COL1A2 are causative in approximately 85% of cases. In recent years, recessive variants in genes involved in collagen processing have been found. Hypodontia (< 6 missing permanent teeth) and oligodontia (≥ 6 missing permanent teeth) have previously been reported in individuals with OI. The aim of the present cross-sectional study was to investigate whether children and adolescents with OI and oligodontia and hypodontia also present with variants in other genes with potential effects on tooth development. The cohort comprised 10 individuals (7.7–19.9 years of age) with known COL1A1/A2 variants who we clinically and radiographically examined and further genetically evaluated by whole-genome sequencing. All study participants were treated at the Astrid Lindgren Children’s Hospital at Karolinska University Hospital, Stockholm (Sweden’s national multidisciplinary pediatric OI team). We evaluated a panel of genes that were associated with nonsyndromic and syndromic hypodontia or oligodontia as well as that had been found to be involved in tooth development in animal models. Results We detected a homozygous nonsense variant in CREB3L1, p.Tyr428*, c.1284C > A in one boy previously diagnosed with OI type III. COL1A1 and COL1A2 were the only two genes among 9 individuals which carried a pathogenic mutation. We found rare variants with unknown significance in several other genes related to tooth development. Conclusions Our findings suggest that mutations in COL1A1, COL1A2, and CREB3L1 may cause hypodontia and oligodontia in OI. The findings cannot exclude additive effects from other modifying or interacting genes that may contribute to the severity of the expressed phenotype. Larger cohorts and further functional studies are needed.http://link.springer.com/article/10.1186/s13023-020-01361-4GeneticsHypodontiaMutationTooth agenesisTooth development |
| spellingShingle | Kristofer Andersson Barbro Malmgren Eva Åström Ann Nordgren Fulya Taylan Göran Dahllöf Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta Orphanet Journal of Rare Diseases Genetics Hypodontia Mutation Tooth agenesis Tooth development |
| title | Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta |
| title_full | Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta |
| title_fullStr | Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta |
| title_full_unstemmed | Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta |
| title_short | Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta |
| title_sort | mutations in col1a1 a2 and creb3l1 are associated with oligodontia in osteogenesis imperfecta |
| topic | Genetics Hypodontia Mutation Tooth agenesis Tooth development |
| url | http://link.springer.com/article/10.1186/s13023-020-01361-4 |
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