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

■ The MCM8 gene is involved in homologous recombination, acting in the ovarian follicles during meiosis II.
■ To the best of our knowledge, this is the first study to report the presence of this variant in a Brazilian woman.
■ The rs138761187 variant had a low incidence; further studies with a larger sample size or focusing on variants at other gene positions may provide insight into the genetic causes of premature ovarian insufficiency.

ABSTRACT

Introduction:

The MCM8 gene is involved in the homologous recombination and repair of doublestranded 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.