Investigation of an MCM8 gene variant in women with premature ovarian insufficiency

Einstein (Sao Paulo). 2024 Nov 22:22:eAO0712. doi: 10.31744/einstein_journal/2024AO0712. eCollection 2024.

Abstract

Introduction: The MCM8 gene is involved in the homologous recombination and repair of double-stranded DNA breaks. It maintains the meiotic process continuously. If the MCM8-9 helicase does not function, the accumulation of DNA breaks can result in cell death. Studies have reported MCM8 gene suppression with primary ovarian insufficiency. In the present study, a variant of the MCM8 gene was investigated in women with primary ovarian insufficiency to elucidate the role of MCM8 in this pathology.

Objective: To evaluate the frequency of the NG_042869.1:g.40270G>A variant of the MCM8 gene in the study population.

Methods: The MCM8 gene variant was analyzed via real-time polymerase chain reaction using a hydrolysis probe in DNA samples from women diagnosed with primary ovarian insufficiency, with a normal karyotype and without FMR1 gene permutation, and from a Control Group, who had menopause after 50 years of age. Frequencies were compared using Fisher's exact test.

Results: A total of 100 samples from the Case Group and 100 samples from the Control Group were selected. The variant was detected in heterozygosity in a Case Group sample but was not identified in the Control Group.

Discussion: This variant was first described in a consanguineous Arab family. This variant is classified as pathogenic and has a prevalence of 1% in women with primary ovarian insufficiency. This study is a pioneering investigation of this variant in Brazilian women.

Conclusion: These findings suggest that the rs138761187 variant of the MCM8 gene is rare in Brazilian women.

Plain language summary

This cross-sectional, case-control study demonstrated that the MCM8 gene might be an autosomal gene implicated in premature ovarian insufficiency. We evaluated the frequency of the NG_042869.1:g.40270G>A (rs138761187) variant in MCM8 in Brazilian women with premature ovarian insufficiency and in those with normal menopause age. This study is a pioneering investigation of the rs138761187 variant of MCM8 in women of Brazilian origin.

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • Genetic Variation / genetics
  • Humans
  • Middle Aged
  • Minichromosome Maintenance Proteins* / genetics
  • Primary Ovarian Insufficiency* / genetics
  • Real-Time Polymerase Chain Reaction

Substances

  • MCM8 protein, human
  • Minichromosome Maintenance Proteins