Abstract
Infantile myofibromatosis (IM) is a benign fibrous tumor of infancy and childhood. A genome-wide linkage analysis and wholeexome sequencing were performed on a pedigree of familial cases, and a mutation in exon 12 of the gene for platelet-derived growth factor receptor beta (PDGFRB) (NM_002609), c.1681C > T p.R561C was identified. This is the first case in a Japanese pedigree, and we detected the mutation of IM in the family by whole-exome sequencing supported by a genome-wide linkage analysis. A wide spectrum of phenotypes was observed among the affected family members despite all having the same mutation. Recently, an additional mutation on the gene for receptor protein tyrosine phosphatase gamma (PTPRG), an enzyme dephosphorylating PDGFRB, was proposed to explain the full phenotypic penetrance in the affected family members with the PDGFRB mutation. However, it is still hypothesized that an additional PDGFRB mutation develops to full activation of PDGFRB in cells that have been primed by p.R561C. The pedigree in this study showed a wide spectrum of phenotypes, suggesting that a second hit, such as with other mutations contributing to PDGFRB phosphorylation, would be necessary to induce IM.
