Abstract
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.
Highlights
Osteogenesis imperfecta (OI) is a genetic connective tissue disorder, with the cardinal symptom being bone fragility, often leading to growth retardation
OI is traditionally classified into four main types according to clinical and radiographic findings [1], where type I is mild with blue sclerae, type II is pre- or perinatally lethal, type III is the most severe type associated with survival of the perinatal period, and type IV is of moderate severity
We found COL1A1 and COL1A2 mutations in 81% of the individuals with OI (123/152; 121 by Sanger sequencing and 2 by multiplex ligation-dependent probe amplification (MLPA))
Summary
Osteogenesis imperfecta (OI) is a genetic connective tissue disorder, with the cardinal symptom being bone fragility, often leading to growth retardation. Affected individuals may have blue sclera, joint laxity, and dentinogenesis imperfecta (DGI or mentioned as DI type I). OI is traditionally classified into four main types according to clinical and radiographic findings [1], where type I is mild with blue sclerae, type II is pre- or perinatally lethal, type III is the most severe type associated with survival of the perinatal period, and type IV is of moderate severity. Collagen I is composed of two α1 chains and one α2 chain, which form a triple helix. Gly-X-Y triplets characterize the helical portion of the α1 and α2 chains, where glycine occurs in every third position, as this is the only residue that fits sterically in the center of the helix. Amino (N)- and carboxy (C)-termini flank the helical domain
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