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Updated: Jun 6, 2025
Using Mouse Oocytes to Assess Human Gene Function During Meiosis I
Published on: April 10, 2018
Investigation of an MCM8 gene variant in women with premature ovarian insufficiency
Beatriz Xavier de Camargo Rabello1, Laura Alves da Rocha1, Caio Parente Barbosa1
1Centro Universitário FMABC, Santo André, SP, Brazil.
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.
Insights
A rare pathogenic variant in the MCM8 gene (rs138761187) was found in 1% of Brazilian women with primary ovarian insufficiency. This MCM8 gene variant was not detected in the control group, suggesting its potential role in this condition.
Area of Science:
- Genetics
- Reproductive Biology
- Molecular Medicine
Background:
- The MCM8 gene is crucial for DNA repair and maintaining meiosis; its dysfunction can lead to DNA breaks and cell death.
- MCM8 gene suppression has been linked to primary ovarian insufficiency (POI).
- This study investigates a specific MCM8 gene variant in women with POI to understand its role.
Purpose of the Study:
- To determine the frequency of the NG_042869.1:g.40270G>A (rs138761187) variant in the MCM8 gene within a Brazilian population experiencing primary ovarian insufficiency.
- To compare the prevalence of this variant between women with POI and a control group.
Main Methods:
- Real-time polymerase chain reaction with hydrolysis probe was used to analyze DNA samples.
- The study included 100 women diagnosed with primary ovarian insufficiency (normal karyotype, no FMR1 permutation) and 100 controls (menopause after age 50).
- Fisher's exact test was employed for frequency comparisons.
Main Results:
- The NG_042869.1:g.40270G>A variant was detected in one sample (1%) from the primary ovarian insufficiency group.
- This specific MCM8 variant was not found in any samples from the control group.
- The variant, classified as pathogenic, was previously identified in a consanguineous Arab family.
Conclusions:
- The rs138761187 variant of the MCM8 gene has a prevalence of 1% in Brazilian women with primary ovarian insufficiency.
- This pathogenic variant appears to be rare in the studied Brazilian population.
- This research represents a pioneering investigation of this MCM8 variant in Brazilian women with POI.
