Reassessing the role of the p.(Arg304Gln) missense AIP variant in pituitary tumorigenesis
Authors' conclusion
Evidence suggests that R304Q is not pathogenic for pituitary neuroendocrine tumour. We recommend changing this variant classification to likely benign and do not recommend pre-symptomatic genetic testing of family members or follow-up of already identified unaffected individuals with the R304Q variant.
Study context
- Population
- Patients with pituitary neuroendocrine tumours carrying the R304Q AIP variant (published cases and International Familial Isolated Pituitary Adenoma Consortium cases)
- Participants
- 38 vs 184
- Exposure
- R304Q AIP variant carriers vs pathogenic/likely pathogenic AIP variant carriers
- R304Qn = 38
- AIPmutn = 184reference
- Outcome
- GH excess
Methodological detailspublished cases plus International Familial Isolated Pituitary Adenoma Consortium cases, comparison with pathogenic/likely pathogenic AIP variant cohort
- Published cases plus International Familial Isolated Pituitary Adenoma Consortium cases
- Comparison with pathogenic/likely pathogenic AIP variant cohort
Main finding
As reported in the abstract
P < 0.001
Observational data: associations, not effects.
Further findings
Age at disease onset · older with R304Q
P < 0.001
Age at diagnosis · older with R304Q
P < 0.001
Population frequency of R304Q
- gnomADv2.1
- 0.31%
- UK Biobank
- 0.16%
- Homozygous R304Q persons
- three
Loss-of-heterozygosity in R304Q tumour samples
- No loss-of-heterozygosity detected in four R304Q pituitary neuroendocrine tumour samples
In silico predictions and experimental data
- In silico predictions and experimental data were conflicting
Original publication
Reassessing the role of the p.(Arg304Gln) missense AIP variant in pituitary tumorigenesis. Eur J Endocrinol. Published 12 March 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →