A Point Mutation in PDGFRB Causes Autosomal-Dominant Penttinen Syndrome

Jennifer J. Johnston, Monica Y. Sanchez-Contreras, Kim M. Keppler-Noreuil, Julie Sapp, Molly Crenshaw, Ni Cole A. Finch, Valerie Cormier-Daire, Rosa Rademakers, Virginia P. Sybert, Leslie G. Biesecker

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Penttinen syndrome is a distinctive disorder characterized by a prematurely aged appearance with lipoatrophy, epidermal and dermal atrophy along with hypertrophic lesions that resemble scars, thin hair, proptosis, underdeveloped cheekbones, and marked acro-osteolysis. All individuals have been simplex cases. Exome sequencing of an affected individual identified a de novo c.1994T>C p.Val665Ala variant in PDGFRB, which encodes the platelet-derived growth factor receptor β. Three additional unrelated individuals with this condition were shown to have the identical variant in PDGFRB. Distinct mutations in PDGFRB have been shown to cause infantile myofibromatosis, idiopathic basal ganglia calcification, and an overgrowth disorder with dysmorphic facies and psychosis, none of which overlaps with the clinical findings in Penttinen syndrome. We evaluated the functional consequence of this causative variant on the PDGFRB signaling pathway by transfecting mutant and wild-type cDNA into HeLa cells, and transfection showed ligand-independent constitutive signaling through STAT3 and PLCγ. Penttinen syndrome is a clinically distinct genetic condition caused by a PDGFRB gain-of-function mutation that is associated with a specific and unusual perturbation of receptor function.

Original languageEnglish (US)
Article number1921
Pages (from-to)465-474
Number of pages10
JournalAmerican journal of human genetics
Issue number3
StatePublished - Sep 3 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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