Journal article

A novel EPAS1/HIF2A germline mutation in a congenital polycythemia with paraganglioma

Felipe R Lorenzo, Chunzhang Yang, Mark Ng Tang Fui, Hariprasad Vankayalapati, Zhengping Zhuang, Huynh Thanh, Mathis Grossmann, Karel Pacak, Josef T Prchal

JOURNAL OF MOLECULAR MEDICINE-JMM | SPRINGER HEIDELBERG | Published : 2013

Abstract

Congenital polycythemias have diverse etiologies, including mutations in the hypoxia sensing pathway. These include HIF2A at exon 12, VHL gene (Chuvash polycythemia), and PHD2 mutations, which in one family was also associated with recurrent pheochromocytoma/paraganglioma (PHEO/PGL). Over the past two decades, we have studied seven unrelated patients with sporadic congenital polycythemia who subsequently developed PHEO/PGL with, until now, no discernible molecular basis. We now report a polycythemic patient with a novel germline HIF2A (F374Y) (exon 9) mutation, inherited from his mother, who developed PHEO/PGL. We show that this is a gain-of-function mutation and demonstrate no loss-of-heter..

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Grants

Awarded by National Health and Medical Research Council of Australia



Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

JTP is supported by NIH-P01CA108671, VA Merit Review Award and University of Utah Seed Grant Program for studies of hypoxic adaptation. MG is supported by a Career Development Fellowship from the National Health and Medical Research Council of Australia (#1006407). KP, ZZ, CY, and TH are supported, in part, by the Intramural Research Program of the NIH, NICHD, and NINDS.