Novel pathogenic mutations in minichromosome maintenance complex component 9 (MCM9) responsible for premature ovarian insufficiency

Three novel missense mutations of MCM9 were identified in Chinese sporadic premature ovarian insufficiency (POI) patients, highlighting the contribution of DNA repair dysfunction in the etiology of POI.

Like Comment
Related Content

Volume 113, Issue 4, Pages 845–852

Authors:

Ting Guo, M.D., Ph.D., Ye Zheng, M.D., Ph.D., Guangyu Li, M.Sc., Shidou Zhao, M.D., Ph.D., Jinlong Ma, M.D., Ph.D., Yingying Qin, M.D., Ph.D.

Abstract:

Objective

To investigate whether mutations in the minichromosome maintenance complex component 9 (MCM9) gene were present in 192 patients with sporadic premature ovarian insufficiency (POI) of Chinese descent.

Design

Genetic and functional study.

Setting

University-based reproductive medicine center.

Patient(s)

A total of 192 patients with sporadic POI and 192 control women with regular menstruation.

Intervention(s)

Sanger sequencing performed in 192 sporadic POI patients, and potential pathogenic variants were excluded in matched controls. Functional effects of mutations on MCM9 were explored based on etoposide-induced DNA damage response, and DNA repair capacity was evaluated by histone H2AX phosphorylation level.

Main Outcome Measure(s)

Sanger sequencing and functional characteristics.

Result(s)

Three novel heterozygous mutations in MCM9, c.C1423T (p.L475F), c.T2921C (p.L974S), and c.G3388A (p.A1130T), were identified in three POI patients separately, which were absent in 192 controls. Functional studies showed that the human embryonic kidney 293 (HEK293) cells overexpressing mutant MCM9 presented with diminished DNA repair capacity compared with wild type.

Conclusion(s)

This study identified novel mutations in MCM9 that are potentially causative for sporadic POI in Chinese women and further highlighted the role of DNA repair capacity in maintenance of ovarian function.


Read the full text here.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

No comments yet.