Heterozygous gain of function variant in GUCY1A2 may cause autonomous ovarian hyperfunction
Authors' conclusion
Our data define a syndromic autonomous ovarian puberty likely due to the activating allele p.(E486D) in GUCY1A2 leading to an increase in cGMP. The overlap with the ovarian symptoms of McCune-Albright syndrome suggests an impact of this cGMP increase on the cAMP pathway in the ovary. Additional cases will be needed to ensure a causal link.
Study context
- Population
- An individual carrying a de novo heterozygous GUCY1A2 variant c.1458G>T p.(E486D), identified by exome sequencingsingle patient
- Participants
- 1 participants
- Comparison
- GUCY1A2 variant α2E486D/β1 vs wild-type enzyme
- Outcome
- Phenotype and enzyme function
Methodological detailsexome sequencing, in vitro functional assays
- Exome sequencing
- In vitro functional assays
Main finding
As reported in the abstract
- Precocious peripheral puberty resembling autonomous ovarian puberty of McCune-Albright syndrome
- Severe intellectual disability
- Increased nitric oxide affinity of mutant enzyme
- Response to carbon monoxide unchanged
- Thermostability decreased vs wild type
- Heme content, susceptibility to oxidation and subcellular localization unchanged
Original publication
Heterozygous gain of function variant in GUCY1A2 may cause autonomous ovarian hyperfunction. Eur J Endocrinol. Published 5 April 2024. doi:10.
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