A schema for sporadic and heritable disease pathogenesis integrating spatiotemporal distribution with the character of genetic variants
Studies on HIF-2α variants have shed light on genotype-phenotype correlations in Pacak-Zhuang syndrome. Here, we propose the combination of the timing of variant acquisition and molecular pathogenicity into a schema to understand phenotypic severity, with implications for other diseases. Alkassi, Cole et al. provide a conceptual framework for understanding how the molecular characteristics and spatiotemporal distribution of HIF2α variants impact the disease phenotype in Pacak–Zhuang Syndrome. This schema has application not only to this syndrome, but also hereditary cancer syndromes and other mosaic diseases.
Authors
- Jared S. Rosenblum (ORCID: https://orcid.org/0000-0001-5941-9082)
- Yasemin Cole (ORCID: https://orcid.org/0000-0002-9492-5885)
- Tara T. Doucet-O’Hare (ORCID: https://orcid.org/0000-0002-1117-2006)
- Zhengping Zhuang (ORCID: https://orcid.org/0000-0002-0009-7370)
- Hussam Alkaissi (ORCID: https://orcid.org/0000-0002-0861-9348)
- Karel Pacák (ORCID: https://orcid.org/0000-0002-3541-3767)
Institutions
- National Institutes of Health (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- Center for Human Genetics (US)
- Institute of Endocrinology (CZ)
- National Cancer Institute (US)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)
- Greenwood Genetic Center (US)
- Clemson University (US)
Publication Details
- Journal
- Communications Medicine
- Published
- 2025-08-08
- DOI
- https://doi.org/10.1038/s43856-025-01039-7
- Citations
- 1
- Primary Topic
- Cancer, Hypoxia, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- National Cancer Institute
- National Institute of Diabetes and Digestive and Kidney Diseases