ESPE Abstracts

Introduction: Premature ovarian insufficiency (POI) is the loss of ovarian activity before the age of 40. POI presents with amenorrhea, hypergonadotropic hypogonadism and infertility. POI can be a part of a syndrome or in isolation and affects up to one in 100 females, including one in 1000 before the age of 30. Abnormalities of the X chromosome or autosomes, autoimmune, infectious, and environmental causes can lead to POI. POI is heritable in up to 30% of individuals. New causatives and proposed relevant candidates have been identified with recent approaches using next generation sequencing (NGS) and whole exome sequencing (WES). To date, more than 50 genes responsible for POI have been identified around the world. A meiotic gene MCM9, have been considered as responsible for Ovarian Dysgenesis 4; POF, short stature, chromosomal instability.

Case: A 14-year-old girl was presented with lack of breast development. She was a product of non-consanguineous marriage and was delivered at term (40-weeks) Her family history was unremarkable except her parents’ consanguineous marriage. 4 years ago, PUVA therapy was applied to her whole body due to vitiligo. On physical examination, weight was 48 kg (-0.7 SDS), height was 153 cm (-1.3 SDS), blood pressure was 110/66 mmHg, and pubertal Tanner stage was compatible with stage 1 for breast development and stage 5 for pubic hair. No Turner stigmata, enlarged clitoris or palpable gonads visualized. She had macules of different sizes all over her body compatible with vitiligo. Other systemic physical examination features were unremarkable. Initial laboratory investigations had shown normal full blood count, electrolytes and renal, liver, thyroid functions. Hormone analysis revealed hypergonadotropic hypogonadism as FSH: 84 mIU/ml LH: 29 mIU/ml and estradiol <5 ng/dl. Bone age was compatible with 13 years and 6 months according to The Greulich and Pyle atlas. The ultrasonographic examination of the pelvis revealed atrophic uterus and streak gonads located in normal positions. Chromosome analysis from peripheral blood cells revealed 46, XX. A homozygous mutation in the MCM9 gene associated with ovarian dysgenesis 4 was detected by Whole Exome Sequencing (WES) analysis. Estrogen replacement therapy was started.

Conclusion: In previous studies, mutations in the MCM9 gene have been shown to be responsible for short stature, POI and chromosomal instability but it has not been reported that vitiligo accompanies in mutations of MCM9 gene. Our findings enrich the MCM9 clinical spectrum.