Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta

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 (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.