ArticleJournal of molecular medicine (Berlin, Germany)2015
Germ-line PHD1 and PHD2 mutations detected in patients with pheochromocytoma/paraganglioma-polycythemia.
Article in Journal of molecular medicine (Berlin, Germany), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 2 syntheses or guidelines pooled it, 143 citations in OpenAlex.
- Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Guideline
- Genotype-phenotype correlations in pheochromocytoma and paraganglioma: a systematic review and individual patient meta-analysis.Endocrine-related cancer · 2019Pooled it
- Familial erythrocytosis associated with anBMJ case reports · 2026Article
- The evolving roles of pathologists in paragangliomas and pheochromocytomas.Virchows Archiv : an international journal of pathology · 2026Review
- Article
- Clinicopathological and genomic analysis of pediatric pheochromocytoma and sympathetic paraganglioma.Endocrine journal · 2025Article
- Non-Susceptibility Gene Variants in Head and Neck Paragangliomas.International journal of molecular sciences · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Deficiency in PHD2-mediated hydroxylation of HIF2α underlies Pacak-Zhuang syndrome.Communications biology · 2024Article
- Oxygen-regulated post-translation modifications as master signalling pathway in cells.EMBO reports · 2023Review
- Characterization of genetic variants in theHaematologica · 2023Article
- Congenital Cyanotic Heart Disease and the Association with Pheochromocytomas and Paragangliomas.Current cardiology reports · 2023Review
- Genome editing and cancer therapy: handling the hypoxia-responsive pathway as a promising strategy.Cellular and molecular life sciences : CMLS · 2023Review
- Rates of Pheochromocytoma/Paraganglioma Screening in At-Risk Populations.The Journal of clinical endocrinology and metabolism · 2023Article
- A Young Patient with Undiagnosed Polycythemia-Paraganglioma Syndrome: A Case Report.The American journal of case reports · 2023Article
- Tumour microenvironment in pheochromocytoma and paraganglioma.Frontiers in endocrinology · 2023Review
- Article
- Novel GermlineMedicina (Kaunas, Lithuania) · 2022Article
- Universal Germline Panel Testing for Individuals With Pheochromocytoma and Paraganglioma Produces High Diagnostic Yield.The Journal of clinical endocrinology and metabolism · 2022Article
- Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
unlabelledWe have investigated genetic/pathogenetic factors associated with a new clinical entity in patients presenting with pheochromocytoma/paraganglioma (PHEO/PGL) and polycythemia. Two patients without hypoxia-inducible factor 2α (HIF2A) mutations, who presented with similar clinical manifestations, were analyzed for other gene mutations, including prolyl hydroxylase (PHD) mutations. We have found for the first time a germ-line mutation in PHD1 in one patient and a novel germ-line PHD2 mutation in a second patient. Both mutants exhibited reduced protein stability with substantial quantitative protein loss and thus compromised catalytic activities. Due to the unique association of patients' polycythemia with borderline or mildly elevated erythropoietin (EPO) levels, we also performed an in vitro sensitivity assay of erythroid progenitors to EPO and for EPO receptor (EPOR) expression. The results show inappropriate hypersensitivity of erythroid progenitors to EPO in these patients, indicating increased EPOR expression/activity. In addition, the present study indicates that HIF dysregulation due to PHD mutations plays an important role in the pathogenesis of these tumors and associated polycythemia. The PHD1 mutation appears to be a new member contributing to the genetic landscape of this novel clinical entity. Our results support the existence of a specific PHD1- and PHD2-associated PHEO/PGL-polycythemia disorder. KEY MESSAGE: • A novel germ-l i n e PHD1 mutation causing heochromocytoma/paraganglioma and polycythemia. • Increased EPOR activity and inappropriate hypersensitivity of erythroid progenitors to EPO.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.