NIH. US: Six
young women with a disorder that mimics menopause have gene
alterations that hamper the repair of damaged DNA, report researchers
supported by the National Institutes of Health. The mutations,
occurring in women with primary ovarian insufficiency (POI),
are in genes that repair damaged DNA in cells of the ovary that
eventually become egg cells. It may also contribute to understanding normal menopause.
The findings may contribute to an
understanding of POI, and to the genetic basis of the precise timing of
menopause that occurs at the usual stage in a woman’s life.
With POI, a woman’s ovaries stop working normally before she is
40 years old — sometimes as early as her teens. The disorder is
thought to affect about 1 percent of women of reproductive age in the
United States. Along with reduced fertility women with POI are also at high risk for osteoporosis and heart disease.
The genetic alterations that the researchers discovered in this
group of patients belong to a family of genes known to help repair
damaged DNA in egg cells — the minichromosome maintenance (MCM) family.
“These studies are the first to link POI to an inability to
repair breaks in the DNA,” said Susan Taymans, Ph.D., of the Fertility
and Infertility Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which funded the study.
The studies appear in the Journal of Clinical Investigation and in the American Journal of Human Genetics.
“Most women with POI don’t know why they have lost their eggs and
can’t reproduce — and this is tragic,” said the senior author of the
studies, Aleksandar Rajkovic, M.D., Ph.D., of the Magee-Womens Research
Institute of the University of Pittsburgh. “Our findings indicate that
genetics may play a strong role in POI, and raise the prospect of one
day developing therapies to delay menopause to an appropriate time in
life.”
To find these mutations, an international team of scientists
performed a series of genetic analyses on blood and skin samples from
the members of three nuclear families. At least one woman in all three
families had POI. The team found that the women with POI in two of the
families had a mutation in the MCM family of genes known as MCM9. The
women with POI in the third family had a mutation in another gene in the
family, MCM8. None of the men in the families had the mutations, nor
did the women who did not have POI.
Dr. Rajkovic explained that MCM8 is involved in early
development of the ovaries and influences the age at which a woman
reaches menopause.
The researchers plan next to investigate whether the MCM8 and
MCM9 mutations play a role in any other health disorders. They also
hope to investigate whether these mutations occur in men, and what
effect they may have on men’s health.
About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The
NICHD sponsors research on development, before and after birth;
maternal, child, and family health; reproductive biology and population
issues; and medical rehabilitation. For more information, visit the
Institute’s website at http://www.nichd.nih.gov.
About the National Institutes of Health (NIH):
NIH, the nation's medical research agency, includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and Human
Services. NIH is the primary federal agency conducting and supporting
basic, clinical, and translational medical research, and is
investigating the causes, treatments, and cures for both common and rare
diseases. For more information about NIH and its programs, visit www.nih.gov.