ClinVar

In affected members of 4 unrelated families with infantile myofibromatosis-1 (IMF1; 228550), Cheung et al. (2013) identified a heterozygous c.1681C-T transition in the PDGFRB gene, resulting in an arg561-to-cys (R561C) substitution at a highly conserved residue. The families were of Chinese, European, French Canadian, and French origin, respectively. The mutation, which was identified by exome sequencing and confirmed by Sanger sequencing in the first 2 families, segregated with the phenotype in all families and was not found in several large control databases. Structural modeling indicated that the R561C mutation occurs in the cytoplasmic juxtamembrane (JM) region between the helical transmembrane segment and the kinase domain, and was predicted to compromise the autoinhibitory role of the JM domain, leading to increased kinase firing and promoting the formation of myofibromas in tissues with high PDGFRB signaling activity. In vitro functional studies were not performed.

Martignetti et al. (2013) identified a heterozygous R561C mutation in the PDGFRB gene in affected members from 7 unrelated families with autosomal dominant infantile myofibromatosis. The mutation, which was identified by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder and was not found in several large control databases.