Genetics of Premature Ovarian Insufficiency: From Molecular Architecture to Precision Medicine.
5 affiliations
- 1Cytogenetics Laboratory, School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
- 2Unit for Multidisciplinary Research in Biomedicine, School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
- 3Stabilité Génétique Cellules Souches et Radiations, LDG/iRCM/IBFJ, Inserm, CEA, Université Paris Cité, F-92260 Fontenay-Aux-Roses, France.
- 4Stabilité Génétique Cellules Souches et Radiations, LDG/iRCM/IBFJ, Inserm, CEA, Université Paris-Saclay, F-92260 Fontenay-Aux-Roses, France.
- 5Unité de Génétique Moléculaire des Maladies Métaboliques et de la Reproduction, Hôpital Bicêtre AP-HP, Hôpitaux Universitaires Paris-Saclay, Faculté de Médecine, Université Paris-Saclay, 94275 Le Kremlin-Bicetre, France.
Abstract
Premature ovarian insufficiency (POI) affects 1-3.7% of women and causes infertility and long-term morbidity. Next-generation sequencing has identified more than 130 POI-associated genes. The diagnostic yield of genetic testing depends on cohort size and the quality and scope of the genetic analysis, reaching 29.3% in our largest international cohort reported to date. Major biological pathways involve meiosis/DNA repair, follicular growth, and mitochondrial/metabolic functions. Meiosis/DNA-repair defects can impair fetal establishment of the ovarian reserve and, depending on the gene, variant, and allelic state, may be associated with chromosomal instability or cancer predisposition. This could enable early identification of selected at-risk patients, oncogenetic assessment, and cancer-prevention strategies. In contrast, alterations affecting follicular growth, metabolism, or mitochondrial function may be associated with persistence of a residual follicular pool, revealing a limited window of opportunity for timely fertility preservation in selected patients and at-risk relatives. Genetic diagnosis provides actionable information for etiological classification, and can reveal a syndromic condition, guide family screening, and, in selected genotypes, inform comorbidity assessment and early fertility preservation. It may also guide future mechanism-based therapies. By translating molecular findings into individualized reproductive and long-term care, POI provides a paradigmatic model of precision medicine in female infertility and reproductive endocrinology.
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BibTeX
@article{sousa2026genetics,
title = {{Genetics of Premature Ovarian Insufficiency: From Molecular Architecture to Precision Medicine.}},
author = {Vanessa Sousa and Gabriel Livera and Micheline Misrahi},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198662},
url = {https://europepmc.org/article/MED/42883908},
note = {CC BY},
}
RIS
TY - JOUR
TI - Genetics of Premature Ovarian Insufficiency: From Molecular Architecture to Precision Medicine.
AU - Vanessa Sousa
AU - Gabriel Livera
AU - Micheline Misrahi
PY - 2026
DA - 2026/09/28
JO - International journal of molecular sciences
DO - 10.3390/ijms27198662
UR - https://europepmc.org/article/MED/42883908
AB - Premature ovarian insufficiency (POI) affects 1-3.7% of women and causes infertility and long-term morbidity. Next-generation sequencing has identified more than 130 POI-associated genes. The diagnostic yield of genetic testing depends on cohort size and the quality and scope of the genetic analysis, reaching 29.3% in our largest international cohort reported to date. Major biological pathways involve meiosis/DNA repair, follicular growth, and mitochondrial/metabolic functions. Meiosis/DNA-repair defects can impair fetal establishment of the ovarian reserve and, depending on the gene, variant, and allelic state, may be associated with chromosomal instability or cancer predisposition. This could enable early identification of selected at-risk patients, oncogenetic assessment, and cancer-prevention strategies. In contrast, alterations affecting follicular growth, metabolism, or mitochondrial function may be associated with persistence of a residual follicular pool, revealing a limited window of opportunity for timely fertility preservation in selected patients and at-risk relatives. Genetic diagnosis provides actionable information for etiological classification, and can reveal a syndromic condition, guide family screening, and, in selected genotypes, inform comorbidity assessment and early fertility preservation. It may also guide future mechanism-based therapies. By translating molecular findings into individualized reproductive and long-term care, POI provides a paradigmatic model of precision medicine in female infertility and reproductive endocrinology.
SN - 1422-0067
ER -