Journal article

Synonymous but Not Silent: A Synonymous VHL Variant in Exon 2 Confers Susceptibility to Familial Pheochromocytoma and von Hippel-Lindau Disease

Shahida K Flores, Ziming Cheng, Angela M Jasper, Keiko Natori, Takahiro Okamoto, Akiyo Tanabe, Koro Gotoh, Hirotaka Shibata, Akihiro Sakurai, Takuya Nakai, Xiaojing Wang, Magnus Zethoven, Shiva Balachander, Yuichi Aita, William Young, Siyuan Zheng, Kazuhiro Takekoshi, Eijiro Nakamura, Richard W Tothill, Ricardo CT Aguiar Show all

The Journal of Clinical Endocrinology & Metabolism | ENDOCRINE SOC | Published : 2019

Abstract

CONTEXT: von Hippel-Lindau disease, comprising renal cancer, hemangioblastoma and/or pheochromocytoma (PHEO) is caused by missense or truncating variants of the VHL tumor suppressor gene, which is involved in degradation of hypoxia inducible factors (HIFs). However, the role of synonymous VHL variants in the disease is unclear. OBJECTIVE: We evaluated a synonymous VHL variant in patients with familial PHEO or VHL disease without a detectable pathogenic VHL mutation. DESIGN: We performed genetic and transcriptional analyses of leukocytes and/or tumors from affected and unaffected individuals and evaluated VHL splicing in existing cancer databases. RESULTS: We identified a synonymous VHL varia..

View full abstract

University of Melbourne Researchers

Grants

Awarded by National Institute of General Medical Sciences, National Institutes of Health


Awarded by NIH National Research Service Award (NRSA) Predoctoral Institutional Training Grants


Awarded by South Texas Medical Scientist Training Program


Awarded by NIH


Awarded by National Center for Advancing Translational Sciences


Awarded by Cancer Prevention and Research Institute of Texas


Awarded by Leukemia and Lymphoma Society


Awarded by Mays Cancer Center at University of Texas Health at San Antonio


Funding Acknowledgements

S.K.F. is currently supported by a National Institute of General Medical Sciences, National Institutes of Health, individual predoctoral fellowship grant (F31-GM131634-01) and previously, by NIH National Research Service Award (NRSA) Predoctoral Institutional Training Grants (T32CA148724). A.M.J. is supported by the South Texas Medical Scientist Training Program (NIH T32GM113896) award. P.L.M.D. receives funding support from NIH (GM114102), Alex's Lemonade Stand Foundation for Childhood Cancer (Innovation Award), and National Center for Advancing Translational Sciences (UL1 TR002645). R.C.T.A. is funded by Cancer Prevention and Research Institute of Texas awards (RP150277, RP170146, and RP190043) and the Leukemia and Lymphoma Society (TRP 6524-17 and VA Merit 10BX001882). The Genomic Sequencing Facility at the Greehey Children's Cancer Research Institute is supported by the Mays Cancer Center at University of Texas Health at San Antonio (P30CA54174) and NIH Shared Instrument Grant 1S10OD021805-01 (S10 grant).