Fig. 1: Radiographic images and pedigrees of families diagnosed with Caffey disease, with identified variants mapped to the triple helical domain of the proα1(I) chain of type I procollagen.

(a) Radiographic images showing hyperostosis of the mandible (upper figure) and clavicle, humerus (distal part), and ulna (lower figure) in proband 19 at age 7 weeks. (b) Radiographic images showing mild hyperostosis and pronounced bowing of the tibia in the proband of family 28 at age 2.5 years. The bowing was improved at age 12 years. (c) Pedigrees of the families in whom DNA of two or more members was analyzed. Full symbol: symptomatic individual. Dotted symbol: asymptomatic individual carrying variant. NA not analyzed. (d) Sanger sequencing identified the previously reported heterozygous variant COL1A1 c.3040C>T, p.(Arg1014Cys), located just outside MLBR-2 in families 1–23, and a novel heterozygous variant COL1A1 c.2752C>T, p.(Arg918Cys), located within MLBR-2 in family 24–28. Ligands binding to procollagen, the proα1(I) chain or the proα2(I) chain are indicated with a full line, a dashed line above the sequence or a dashed line below the sequence, respectively. Scissors: MMP-1 cleavage site. APP amyloid precursor protein, COMP cartilage oligomeric matrix protein, DDR2 discoidin domain receptor 2, HSP47 heat shock protein 47, MLBR-2 major ligand binding region, MMP matrix metalloproteinase, SPARC secreted protein acidic and rich in cysteine binding site, THP/α1 α2β1 triple helical peptide binds integrin receptors, THP/FA+ triple helical peptide promotes fibroblast adhesion. Figure adapted from Sweeney et al. [14].