FMR1 allelic complexity in premutation carriers provides no evidence for a correlation with age at amenorrhea.

Autor: Rodrigues B; Molecular Genetics Laboratory, Laboratory Genetics Service, Genetics and Pathology Clinic, Unidade Local de Saúde de Santo António (ULSSA), Porto, Portugal.; UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS - School of Medicine and Biomedical Sciences, UPorto - University of Porto, Porto, Portugal.; ITR - Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal., Sousa V; Molecular Genetics Laboratory, Laboratory Genetics Service, Genetics and Pathology Clinic, Unidade Local de Saúde de Santo António (ULSSA), Porto, Portugal.; UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS - School of Medicine and Biomedical Sciences, UPorto - University of Porto, Porto, Portugal.; ITR - Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal.; Cytogenetics Laboratory, Department of Microscopy, ICBAS - School of Medicine and Biomedical Sciences, UPorto - University of Porto, Porto, Portugal., Yrigollen CM; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia Research Institute, Philadelphia, PA, USA., Tassone F; Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Stockton Blvd, USA.; MIND Institute, School of Medicine, University of California, Davis, CA, USA., Villate O; Pediatric Oncology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, Biscay, Basque Country, Spain., Allen EG; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA., Glicksman A; New York State Institute for Basic Research in Developmental Disabilities, New York, NY, USA., Tortora N; New York State Institute for Basic Research in Developmental Disabilities, New York, NY, USA., Nolin SL; New York State Institute for Basic Research in Developmental Disabilities, New York, NY, USA., Nogueira AJA; CESAM - Center for Environmental and Marine Studies, Department of Biology, University of Aveiro, Aveiro, Portugal., Jorge P; Molecular Genetics Laboratory, Laboratory Genetics Service, Genetics and Pathology Clinic, Unidade Local de Saúde de Santo António (ULSSA), Porto, Portugal. paulajorge.icbas@gmail.com.; UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS - School of Medicine and Biomedical Sciences, UPorto - University of Porto, Porto, Portugal. paulajorge.icbas@gmail.com.; ITR - Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal. paulajorge.icbas@gmail.com.; Cytogenetics Laboratory, Department of Microscopy, ICBAS - School of Medicine and Biomedical Sciences, UPorto - University of Porto, Porto, Portugal. paulajorge.icbas@gmail.com.
Jazyk: angličtina
Zdroj: Reproductive biology and endocrinology : RB&E [Reprod Biol Endocrinol] 2024 Jun 21; Vol. 22 (1), pp. 71. Date of Electronic Publication: 2024 Jun 21.
DOI: 10.1186/s12958-024-01227-5
Abstrakt: Background: Premutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, defined as between 55 and 200 CGGs, have been implicated in fragile X-associated primary ovarian insufficiency (FXPOI). Only 20% of female premutation carriers develop early ovulatory dysfunction, the reason for this incomplete penetrance is unknown. This study validated the mathematical model in premutation alleles, after assigning each allele a score representing allelic complexity. Subsequently, allelic scores were used to investigate the impact of allele complexity on age at amenorrhea for 58 premutation cases (116 alleles) previously published.
Methods: The allelic score was determined using a formula previously described by our group. The impact of each allelic score on age at amenorrhea was analyzed using Pearson's test and a contour plot generated to visualize the effect.
Results: Correlation of allelic score revealed two distinct complexity behaviors in premutation alleles. No significant correlation was observed between the allelic score of premutation alleles and age at amenorrhea. The same lack of significant correlation was observed regarding normal-sized alleles, despite a nearly significant trend.
Conclusions: Our results suggest that the use of allelic scores combination have the potential to explain female infertility, namely the development of FXPOI, or ovarian dysfunction, despite the lack of correlation with age at amenorrhea. Such a finding is of great clinical significance for early identification of females at risk of ovulatory dysfunction, enhancement of fertility preservation techniques, and increasing the probability for a successful pregnancy in females with premutations. Additional investigation is necessary to validate this hypothesis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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