ESPE Abstracts

Introduction: Primary ovarian insufficiency (POI) is a condition characterized by amenorrhea with elevated FSH and LH levels as a result of ovarian dysfunction. Ovarian failure is a very rare condition in pediatric population. Genetic syndromes (Turner, Fragile X syndrome) or malignancy treatment are the main reasons. The minichromosome maintenance complex component 8 (MCM8) gene is responsible for the repair of DNA double-strand breaks;MCM8 is a rare cause of primary ovarian insufficiency (POI) in adolescents and children. In this report, a case of POI who presented with delayed puberty and was diagnosed with a novel homozygous variant in the MCM8 gene is presented.

Case: A 14-year-old girl came to our clinic due to delayed puberty and lack of menstruation. There was no feature in her history. There was no consanguinity clearly stated in her family history. There were maternal and paternal relatives who complained of infertility and amenorrhoea. On physical examination, the patient's body weight was 60 kg (+1.46 SD), height: 153.5 cm (-0.42 SD), and her systemic examination was normal. In the pubertal examination, breast development was Tanner stage 1, pubic and axillary hair growth was Tanner stage 3. In the examinations, serum FSH: 83 U/L, LH: 41 IU/L, Estradiol:<5 ng/L, AMH <0.01 ng/ml and thyroid function tests were within the normal range. The patient's findings were consistent with hypergonadotropic hypogonadism. The uterine long axis was measured as 38 mm in pelvic ultrasonography and the ovaries could not be visualized. Karyotype determination in peripheral blood was reported as 46,XX and no premutation was detected in the FMR1 gene. The patient's treatment was arranged as estrogen and progestin therapy In the next generation sequence analysis, a novel homozygous c.2120G>C (p.Arg707Pro) variant was detected in the MCM8 gene, and in silico analyzes confirmed that the variant was pathogenic. In the segregation analysis, the same variant in the MCM8 gene was detected as heterozygous in her parents and two siblings. Signs of short stature, hypothyroidism, malignancy that may present MCM8 mutations were not found in our case. The patient was followed up for possible ovarian malignancies that might develop in the future. With the treatment, secondary sexual characteristics developed in line with her age and her menstrual cycles were continued regularly.

Conclusion: Pathogenic variants in the MCM8 gene are one of the rare genetic causes of POI. Finding the genes responsible for etiology is important for the clinical management of POI, preventing ovarian damage, maintaining fertility and oocyte cryopreservation, and determining the risk of malignancy.