A team of doctors from Saudi Arabia and the United States has identified a specific gene mutation that is linked to premature ovarian failure (POF), a form of early menopause that leaves a woman infertile before the age of 40. The specific gene — MCM8 — is part of a family of genes associated with the DNA replication process. The mutation in MCM8 was found to be directly linked to POF.
Dr. Aleksandar Rajkovic led the study based at the University of Pittsburgh, Pennsylvania. The research team examined the genomes of three sisters who suffered POF and compared them with the genomes of their sisters without the disorder, their brothers, and their parents.
There were 12 children (seven daughters, five sons) in the family under study. The first child was 35 at the time of study and she had POF. Child #6 (24 years old) and Child #9 (19 years old) also had POF.
The mother’s reproductive years were reported as normal: first period at age 14, regular menstrual cycle until her mid-40s, and last documented menstrual period at age 49. At the time of study, her 12 children ranged in age from 14 to 35. The three sisters affected by POF experienced:
- Amenorrhea (abnormal absence of menstrual cycle)
- Hypoestrogenic symptoms (hot flashes, premature osteoporosis, vaginal dryness, and other symptoms commonly associated with menopause)
- Hypothyroidism (low-functioning thyroid gland)
- Underdeveloped uterus
- Abnormally small ovaries
The research team found no evidence that the three sisters with POF had any other disorders that might cause these symptoms.
The parents of the children were first cousins. Both parents had one copy each of the POF-inducing MCM8 gene variant, possibly inherited from a common ancestor. The three sisters with POF had two copies of it, indicating they inherited the same gene mutation from each parent. Two healthy sisters and two brothers each had one copy of the gene variant. The remaining five siblings did not carry the MCM8 gene mutation.
To confirm the genetic nature of the MCM8 mutation, DNA sequencing was conducted on samples donated by 200 fertile female volunteers. None of them carried the MCM8 gene mutation.
According to the US National Institutes of Health, POF is also known as ovarian insufficiency and primary ovarian insufficiency. It differs from premature menopause in that women diagnosed with premature menopause stop having periods before age 40 and cannot become pregnant; women with POF do experience occasional periods after age 40 and can become pregnant although the probability is quite small. Premature menopause can occur spontaneously or be the result of disease or surgery or from treatments using radiation or chemotherapy while the cause of POF has historically been unknown.
- AlAsiri, Saleh, et al. “Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability.” JCI / The Journal of Clinical Investigation. The American Society for Clinical Investigation. 1 Dec. 2014. Web. 12 Dec. 2014.
- National Institute of Child Health and Human Development. “Premature Ovarian Failure.” MedlinePlus. US National Library of Medicine. 22 Jul. 2014. Web. 12 Dec. 2014.