{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:47:36Z","timestamp":1783435656610,"version":"3.54.6"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,2,15]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Activating variants in platelet\u2010derived growth factor receptor beta (PDGFRB), including a variant we have previously described (p.Tyr562Cys [g.149505130T&gt;C [GRCh37\/hg19]; c.1685A&gt;G]), are associated with development of multiorgan pathology, including aneurysm formation. To investigate the association between the allele fraction genotype and histopathologic phenotype, we performed an expanded evaluation of post\u2010mortem normal and aneurysmal tissue specimens from the previously published index patient.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Following death due to diffuse subarachnoid hemorrhage in a patient with mosaic expression of the above PDGFRB variant, specimens from the intracranial, coronary, radial and aortic arteries were harvested. DNA was extracted and alternate allele fractions (AAF) of\n              <jats:italic>PDGFRB<\/jats:italic>\n              were determined using digital droplet PCR. Radiographic and histopathologic findings, together with genotype expression of\n              <jats:italic>PDGFRB<\/jats:italic>\n              were then correlated in aneurysmal tissue and compared to non\u2010aneurysmal tissue. The\n              <jats:italic>PDGFRB<\/jats:italic>\n              variant was identified in the vertebral artery, basilar artery, and P1 segment aneurysms (AAF: 28.7%, 16.4%, and 17.8%, respectively). It was also identified in the coronary and radial artery aneurysms (AAF: 22.3% and 20.6%, respectively). In phenotypically normal intracranial and coronary artery tissues, the\n              <jats:italic>PDGFRB<\/jats:italic>\n              variant was not present. The\n              <jats:italic>PDGFRB<\/jats:italic>\n              variant was absent from lymphocyte DNA and normal tissue, confirming it to be a non\u2010germline somatic variant. Primary cell cultures from a radial artery aneurysm localized the\n              <jats:italic>PDGFRB<\/jats:italic>\n              variant to CD31\u2010, non\u2010endothelial cells.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Constitutive expression of PDGFRB within the arterial wall is associated with the development of human fusiform aneurysms. The role of targeted therapy with tyrosine kinase inhibitors in fusiform aneurysms with\n              <jats:italic>PDGFRB<\/jats:italic>\n              mutations should be further studied.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.024289","type":"journal-article","created":{"date-parts":[[2022,2,12]],"date-time":"2022-02-12T10:59:03Z","timestamp":1644663543000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Somatic Mosaicism of a PDGFRB Activating Variant in Aneurysms of the Intracranial, Coronary, Aortic, and Radial Artery Vascular Beds"],"prefix":"10.1161","volume":"11","author":[{"given":"Carolina A.","family":"Parada","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery University of Washington School of MedicineUniversity of Washington Medical Center Seattle WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima M.","family":"El\u2010Ghazali","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery University of Washington School of MedicineUniversity of Washington Medical Center Seattle WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne","family":"Toglia","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery University of Washington School of MedicineUniversity of Washington Medical Center Seattle WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Ruzevick","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery University of Washington School of MedicineUniversity of Washington Medical Center Seattle WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malia","family":"McAvoy","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery University of Washington School of MedicineUniversity of Washington Medical Center Seattle 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A.","family":"Nazem","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery University of Washington School of MedicineUniversity of Washington Medical Center Seattle WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun M.","family":"Suranowitz","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery University of Washington School of MedicineUniversity of Washington Medical Center Seattle WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8501-2750","authenticated-orcid":false,"given":"Sherene","family":"Shalhub","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery University of Washington School of MedicineUniversity of Washington Medical Center Seattle WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2601-6276","authenticated-orcid":false,"given":"Desiree 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