| Autor: |
Chunzhang Yang, Thanh-Truc Huynh, Garima Gupta, Herui Wang, Zhengping Zhuang, Karel Pacak, Abhishek Jha, Emily Y. Chew, Esther Korpershoek, Xupeng Yue, Ying Pang, Richard A Feelders, Eva H. Baker, Aiguo Li |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Journal of the Endocrine Society |
| ISSN: |
2472-1972 |
| Popis: |
Background: Somatic mutations in hypoxia-inducible factor 2α (HIF2A) is associated with polycythemia-paraganglioma syndrome. Specifically, the classic presentation of female patients with recurrent paragangliomas (PGLs), polycythemia (at birth or in early childhood), and duodenal somatostatinomas has been described. Studies have demonstrated that somatic HIF2A mutations occur as postzygotic events and some to be associated with somatic mosaicism affecting hematopoietic and other tissue precursors. This phenomenon could explain the development of early onset of polycythemia in the absence of erythropoietin secreting tumors. Methods: Correlation analysis was performed between mosaicism of HIF2A mutant patients and clinical presentations. Results: Somatic HIF2A mutations (p.A530V, p.P531S and p.D539N) were identified in DNA extracted from PGLs of three patients. No somatic mosaicism was detected through deep sequencing of blood genomic DNA. Compared to classic syndrome, both polycythemia and PGL in all three patients developed at an advanced age with polycythemia at 30, 30, and 17 and PGLs at age 34, 30, and 55 years, respectively. Somatostatinomas were not detected and two patients had ophthalmic findings. The biochemical phenotype in all three patients was noradrenergic with 18F-fluorodopa PET/CT as the most sensitive imaging modality. All patients demonstrated multiplicity and none developed metastatic disease. Conclusions: These findings suggest that newer techniques need to be developed to detect germline or somatic mosaicism in patients with this syndrome. Absence of HIF2A mosaicism in patients with somatic HIF2A mutations supports association with late onset of the disease, milder clinical phenotype and an improved prognosis compared to patients with HIF2A mosaicism. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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