Mutation in TGFB1 Causes Rare Progressive Diaphyseal Dysplasia

  Objective  To investigate the phenotypes of a kindred with progressive diaphyseal dysplasia (PDD) and to detect the mutation of transforming growth factor beta-1 (TGFB1) gene.

  Methods  A PDD patient of a non-consanguineous family presented with early onset in childhood, who suffered from lower limb pain, fatigability and muscle weakness. Her clinical manifestations, features of skeletal X-ray examination, and bone turnover markers were evaluated. Mutation of TGFB1 was identified by direct Sanger sequencing of polymerase chain reaction amplification product.

  Results  The proband presented with elevated bone turnover biomarkers, and nonuniform thickening and sclerosis of bone cortex of limbs in X-ray films. A heterozygous missense mutation c.652C > T(p.Arg218Cys) in exon 4 of TGFB1 was identified in the proband, but not in either of her parents. Glucocorticoid was given and after 4 months of treatment, the bone pain and activity were obviously improved.

  Conclusions  The typical clinical manifestations of PDD are limb pain and diaphyseal hyperostosis. The missense mutations at position 218 of TGFB1 are hotspot pathogenic mutations of PDD. Glucocorticoids can mitigate the symptoms in PDD patients.