Camurati-Engelmann disease (CED [MIM 131300]), or progressive diaphyseal dysplasia, is an autosomal dominant sclerosing bone dysplasia characterized by progressive bone formation along the periosteal and endosteal surfaces at the diaphyseal and metaphyseal regions of long bones and cranial hyperostosis, particularly at the skull base.
We conclude that CED is a clinically variable condition and that this clinical variability is not accounted for by polymorphisms at the TGF-beta1 locus.
We recently reported that three different missense mutations (R218H, R218C, and C225R) of beta1-LAP cause the Camurati-Engelmann disease (CED), an autosomal dominant disorder characterized by hyperosteosis and sclerosis of the diaphysis of the long bones.
We recently found mutations of the transforming growth factor beta 1 (TGF-beta1) gene (TGFB1) in 9 families, in which progressive diaphyseal dysplasia (Camurati-Engelmann disease) is segregating [Kinoshita et al., 2000: Nat Genetics 26:19-20].
Osteoclast formation was enhanced approximately 5-fold (P < 0.001) and bone resorption approximately 10-fold (P < 0.001) in CED patients, and the increase in osteoclast formation was inhibited by soluble TGFbeta type II receptor.
Our data indicate that the mutations in the signal peptide and latency-associated peptide facilitate TGF-beta1 signaling, thus causing Camurati-Engelmann disease.
For all 100 cases, molecular evidence for CED was available, as a mutation was detected in TGFB1, the gene encoding transforming growth factor (TGF) beta1.
Both individuals were heterozygous for a novel 12-bp duplication (c.27_38dup, p.L10_L13dup) in exon 1 of TGFβ1, predicting four additional leucine residues in the latency-associated-peptide segment of TGFβ1, consistent with CED.