PGT-M for Premature Ovarian Failure Related to CGG Repeat Expansion of the FMR1 Gene

Tiziana Persico; Maria Lucrezia Tranquillo; Renato Seracchioli; Daniela Zuccarello; Ugo Sorrentino

doi:10.3390/genes15010006

PGT-M for Premature Ovarian Failure Related to CGG Repeat Expansion of the FMR1 Gene

Genes (Basel). 2023 Dec 19;15(1):6. doi: 10.3390/genes15010006.

Authors

Tiziana Persico¹, Maria Lucrezia Tranquillo², Renato Seracchioli^{2

3}, Daniela Zuccarello⁴, Ugo Sorrentino⁴

Affiliations

¹ Medically Assisted Procreation Center, Maternal and Child Department, Beauregard Hospital, Valle D'Aosta Local Public Health, 11100 Aoste, Italy.
² Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy.
³ Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero, University of Bologna, 40138 Bologna, Italy.
⁴ Clinical Genetics and Epidemiology Unit, University of Padova, 35128 Padova, Italy.

Abstract

Primary ovarian failure (POF) is caused by follicle exhaustion and is associated with menstrual irregularities and elevated gonadotropin levels, which lead to infertility before the age of 40 years. The etiology of POI is mostly unknown, but a heterogeneous genetic and familial background can be identified in a subset of cases. Abnormalities in the fragile X mental retardation 1 gene (FMR1) are among the most prevalent monogenic causes of POI. These abnormalities are caused by the expansion of an unstable CGG repeat in the 5' untranslated region of FMR1. Expansions over 200 repeats cause fragile X syndrome (FXS), whereas expansions between 55 and 200 CGG repeats, which are defined as a fragile X premutation, have been associated with premature ovarian failure type 1 (POF1) in heterozygous females. Preimplantation genetic testing for monogenic diseases (PGT-M) can be proposed when the female carries a premutation or a full mutation. In this narrative review, we aim to recapitulate the clinical and molecular features of POF1 and their implications in the context of PGT-M.

Keywords: FMR1; FMR1 premutation; FXPOI; IVF; POF1; fragile X syndrome; preimplantation genetic testing; premature ovarian failure.

Publication types

Review

MeSH terms

5' Untranslated Regions
Alleles
Female
Fragile X Mental Retardation Protein / genetics
Fragile X Syndrome* / genetics
Genetic Testing
Humans
Mutation
Primary Ovarian Insufficiency* / genetics

Substances

5' Untranslated Regions
FMR1 protein, human
Fragile X Mental Retardation Protein

Grants and funding

This work was supported by European Union-Next Generation EU-PNRR M6C2-Investimento 2.1 Valorizzazione e potenziamento della ricerca biomedica del SSN (grant number PNRR-MR!-2022-12376108).