The platelet-derived growth factor receptor beta (PDGFRB) gene is involved in proliferative and developmental processes in mammals. Variations in this gene lead to several different syndromic conditions, such as infantile myofibromatosis I, sporadic port-wine stain, primary familial brain calcification, and the Penttinen and overgrowth syndromes. Our objective was to investigate PDGFRB’s genetic relationship to clinical conditions and evaluate the protein interactions using GeneNetwork, GeneMANIA, and STRING network databases. We have evidenced the gene’s pleiotropy through its many connections and its link to syndromic conditions. Therefore, PDGFRB may be an important therapeutic target for treating such conditions.
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Al Qawahmed R, Sawyer SL, Vassilyadi M, Qin W, Boycott KM, Michaud J (2018) Infantile myofibromatosis with intracranial extradural involvement and PDGFRB mutation: a case report and review of the literature. Pediatr Dev Pathol 22:58–264. https://doi.org/10.1177/1093526618787736
Arts FA, Sciot R, Brichard B, Renard M, de Rocca Serra A, Dachy G et al (2017) PDGFRB gain-of-function mutations in sporadic infantile myofibromatosis. Hum Mol Genet 26(10):1801–1810. https://doi.org/10.1093/hmg/ddx081
Cheung YH, Gayden T, Campeau PM, LeDuc CA, Russo D, Nguyen V-H et al (2013) A recurrent PDGFRB mutation causes familial infantile myofibromatosis. Am J Hum Genet 92(6):996–1000. https://doi.org/10.1016/j.ajhg.2013.04.026
Deelen P, van Dam S, Herkert JC, Karjalainen JM, Brugge H, Abbott KM, et al (2018) Improving the diagnostic yield of exome-sequencing, by predicting gene-phenotype associations using large-scale gene expression analysis. bioRxiv. https://doi.org/10.1101/375766
Gawlinski P, Pelc M, Ciara E, Jhangiani S, Jurkiewicz E, Gambin T et al (2018) Phenotype expansion and development in Kosaki overgrowth syndrome. Clin Genet 93(4):919–924. https://doi.org/10.1111/cge.13192
Hellstrom M, Kalen M, Lindahl P, Abramsson A, Betsholtz C (1999a) Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development (Cambridge, England) 126(14):3047–3055
Hewitt KJ, Shamis Y, Knight E, Smith A, Maione A, Alt-Holland A et al (2012) PDGFRbeta expression and function in fibroblasts derived from pluripotent cells is linked to DNA demethylation. J Cell Sci 125(Pt 9):2276–2287. https://doi.org/10.1242/jcs.099192
Johnston JJ, Sanchez-Contreras MY, Keppler-Noreuil KM, Sapp J, Crenshaw M, Finch NA et al (2015) A point mutation in PDGFRB causes autosomal-dominant Penttinen syndrome. Am J Hum Genet 97(3):465–474. https://doi.org/10.1016/j.ajhg.2015.07.009
Lian CG, Sholl LM, Zakka LR, Teresa MO, Liu C, Xu S et al (2014) Novel genetic mutations in a sporadic port-wine stain. JAMA Dermatology 150(12):1336–1340. https://doi.org/10.1001/jamadermatol.2014.1244
Lindahl P, Johansson BR, Levéen P, Betsholtz C (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277(5323):242 LP-242245. Retrieved from http://science.sciencemag.org/content/277/5323/242.abstract
Martignetti JA, Tian L, Li D, Ramirez MCM, Camacho-Vanegas O, Camacho SC et al (2013) Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. Am J Hum Genet 92(6):1001–1007. https://doi.org/10.1016/j.ajhg.2013.04.024
Nicolas G, Pottier C, Maltete D, et al (2013) Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification. Neurology 80:181–187. https://doi.org/10.1212/WNL.0b013e31827ccf34
Paaby AB, Rockman MV (2013) The many faces of pleiotropy. Trends Genet 29(2):66–73. https://doi.org/10.1016/j.tig.2012.10.010
Pond D, Arts FA, Mendelsohn NJ, Demoulin J-B, Scharer G, Messinger Y (2018) A patient with germ-line gain-of-function PDGFRB p.N666H mutation and marked clinical response to imatinib. Genet Med 20(1):142–150. https://doi.org/10.1038/gim.2017.104
Raso A, Biassoni R, Mascelli S, Nozza P, Ugolotti E, DI Marco E et al (2016) Moyamoyavasculopathy shows a genetic mutational gradient decreasing from East to West. J Neurosurg Sci
Roder C, Peters V, Kasuya H, Nishizawa T, Takehara Y, Berg D et al (2010) Polymorphisms in TGFB1 and PDGFRB are associated with Moyamoya disease in European patients. Acta Neurochir 152(12):2153–2160. https://doi.org/10.1007/s00701-010-0711-9
Sanchez-Contreras M, Baker MC, Finch NA, Nicholson A, Wojtas A, Wszolek ZK et al (2014) Genetic screening and functional characterization of PDGFRB mutations associated with basal ganglia calcification of unknown etiology. Hum Mutat 35(8):964–971. https://doi.org/10.1002/humu.22582
Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J et al (2015) STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43(Database issue):D447–D452. https://doi.org/10.1093/nar/gku1003
Takenouchi T, Yamaguchi Y, Tanikawa A, Kosaki R, Okano H, Kosaki K (2015) Novel overgrowth syndrome phenotype due to recurrent de novo PDGFRB mutation. J Pediatr 166(2):483–486. https://doi.org/10.1016/j.jpeds.2014.10.015
Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P et al (2010) The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res 38(Web Server issue):W214–W220. https://doi.org/10.1093/nar/gkq537
Winkler EA, Bell RD, Zlokovic BV (2010) Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling. Mol Neurodegener 5:32. https://doi.org/10.1186/1750-1326-5-32
Yavarna T, Al-Dewik N, Al-Mureikhi M, Ali R, Al-Mesaifri F, Mahmoud L et al (2015) High diagnostic yield of clinical exome sequencing in middle eastern patients with Mendelian disorders. Hum Genet 134(9):967–980. https://doi.org/10.1007/s00439-015-1575-0
Zhang Z, Zheng S, Zheng S, Wang Y, Xu X-G, Gao X-H, Chen H-D (2018) Premature aging syndrome, Penttinen type: report of a Chinese case with a PDGFRB mutation. ActaDermato-Venereologica 98(9):912–913. https://doi.org/10.2340/00015555-2993
Zhong CS, Song H, Weiss A, Tan W-H, Coury S, Huang JT (2018, December) Myofibromatosis presenting as reticulated vascular changes and subcutaneous atrophy in a patient with somatic mosaicism of PDGFRB mutation. Br J Dermatol. https://doi.org/10.1111/bjd.16995
We would like to thank the Brazilian funding agency FACEPE (IBPG-0465-2.02/17) for financial support during this project.
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Moura, D.A.P., de Oliveira, J.R.M. The Master of Puppets: Pleiotropy of PDGFRB and its Relationship to Multiple Diseases. J Mol Neurosci (2020). https://doi.org/10.1007/s12031-020-01618-4
- Molecular network
- Complex diseases