Estimated global prevalence of genetic carriers of hereditary pheochromocytoma-paraganglioma syndrome in a large multiethnic genomic database
Authors' conclusion
Our study highlights the variability in PPGL-associated mutation carrier prevalence across genes and ancestries. The findings underscore potential disparities in genetic risk that may not have been fully captured by clinical cohorts.
Study context
- Population
- Unrelated individuals of diverse ethnic ancestries in the gnomAD v4.1 database; 11 PPGL-associated genes (FH, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL, MAX)
- Participants
- 807,162 unrelated individuals
- Outcome
- Prevalence of genetic carriers of PPGL syndromes (ClinVar P/LP and predicted deleterious variants)
Methodological detailsgenomic database analysis, multiethnic
- Genomic database analysis
- Multiethnic
Main finding
As reported in the abstract
Carrier prevalence (ClinVar P/LP + predicted deleterious variants)
SDHA carriers (highest)
158.83 per 100 000
NF1 carriers
93.66 per 100 000
FH carriers
72.23 per 100 000
Observational data: associations, not effects.
Further findings
Variation across ancestries
- Substantial variation across ancestries; certain variants enriched in specific populations (eg, SDHC p.Tyr126Cys in non-Finnish Europeans; FH c.556-4A > G in East Asians)
- SDHB, SDHC and TMEM127 carriers absent in Middle Eastern group
- SDHAF2 and SDHC absent in Ashkenazi Jewish group
- SDHAF2 and TMEM127 absent in Finnish group
Contribution of predicted deleterious variants
- Predicted deleterious variants significantly increased carrier estimates for SDHAF2, SDHD and TMEM127
Original publication
Estimated global prevalence of genetic carriers of hereditary pheochromocytoma-paraganglioma syndrome in a large multiethnic genomic database. Eur J Endocrinol. Published 17 September 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →