Familial PDGFRA-mutation syndrome: somatic and gastrointestinal phenotype.
Germline activating platelet-derived growth factor receptor alpha (PDGFRA) mutations have been described in four families. All the index patients have presented with multiple mesenchymal tumors of the gastrointestinal tract. We identified a fifth family with four first-degree relatives that harbor a PDGFRA exon 18 (D846V) germline mutation. The affected kindred have a unique phenotype including coarse facies and skin, broad hands and feet, and previously undescribed premature tooth loss. While the index patient presented with multiple small bowel inflammatory fibroid polyps (IFPs) and has a gastric gastrointestinal stromal tumor (GIST), no tumors have yet been identified in other family members. We describe the pathology, genetics, the incomplete penetrance and variable expressivity of the familial PDGFRA-mutation syndrome referencing the mouse knock-in Pdgfra model. We speculate on the role of the telocyte, a recently described CD34, PDGFRA+ stromal cell, in the development of inflammatory fibroid polyps and the somatic phenotype.
['Manley|Paul N|PN|', 'Abu-Abed|Suzy|S|', 'Kirsch|Richard|R|', 'Hawrysh|Andrea|A|', 'Perrier|Nicole|N|', 'Feilotter|Harriet|H|', 'Pollett|Aaron|A|', 'Riddell|Robert H|RH|', 'Hookey|Lawrence|L|', 'Walia|Jagdeep S|JS|']
D000328:Adult D000818:Animals D014408:Biomarkers, Tumor D001706:Biopsy D004252:DNA Mutational Analysis D005091:Exons D005260:Female D005770:Gastrointestinal Neoplasms D046152:Gastrointestinal Stromal Tumors D055879:Gene Knock-In Techniques D020022:Genetic Predisposition to Disease D018095:Germ-Line Mutation D040941:Heredity D006801:Humans D007417:Intestinal Polyps D008297:Male D008822:Mice, Transgenic D008875:Middle Aged D009386:Neoplastic Syndromes, Hereditary D010375:Pedigree D010641:Phenotype D020796:Receptor, Platelet-Derived Growth Factor alpha D000067170:Telocytes
PDGFRA Inflammatory fibroid polyp GIST Telocyte Dysmophology