Clinical and Genetic Investigation of Premature Ovarian Insufficiency Cases from Turkey - 04/05/19

Doi : 10.1016/j.jogoh.2019.04.007

Engin Oral ^a,^{^{1
These authors contributed equally to this study.}} , Guven Toksoy ^b,^{^{1
These authors contributed equally to this study.}} , Nigar Sofiyeva ^a,^{^{2
Present address: Mayo Clinic, Department of Obstetrics and Gynecology, Rochester, MN, USA.}} , Hale Goksever Celik ^c,^⁎ , Birsen Karaman ^b , Seher Basaran ^b , Asli Azami ^a , Zehra Oya Uyguner ^b
^a Istanbul University, Cerrahpasa Medical Faculty, Department of Obstetrics and Gynecology, Istanbul, Turkey
^b Istanbul University, Istanbul Medical Faculty, Department of Medical Genetics, Turkey
^c Saglik Bilimleri University Istanbul Kanuni Sultan Suleyman Training and Research Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey

^⁎Corresponding author at: Saglik Bilimleri University Istanbul Kanuni Sultan Suleyman Training and Research Hospital, Turgut Ozal Boulevard, No: 1, Kucukcekmece, Istanbul, Turkey.Saglik Bilimleri University Istanbul Kanuni Sultan Suleyman Training and Research HospitalTurgut Ozal Boulevard, No: 1, KucukcekmeceIstanbulTurkey

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Abstract

Objective

Premature ovarian insufficiency is a lack of ovarian functions in patients younger than 40 years old. Genetic causes leading to accelerated follicle depletion may result in premature ovarian insufficiency. We aimed to determine genetic etiology of nonsyndromic premature ovarian insufficiency cases from Turkey.

Materials and methods

We analyzed 86 nonsyndromic premature ovarian insufficiency cases and 26 matched control female participants. Participants have been investigated in cytogenetic analysis followed by FMR1 repeat size expansions and search of variants for nine premature ovarian insufficiency-associated genes.

Results

Four cases had a structural cytogenetic abnormality. Two cases revealed with premutation size FMR1 triplet repeat expansion. Four cases carried variants in which two were very rare in FSHR and PDPK1, and three were novel in NR5A1, PDPK1, and POF1B genes. Six novel variants have been identified in NOBOX, NR5A1, POF1B, and PDPK1 in control population assigned to be benign alterations.

Conclusion

Mosaicism of sex chromosomes was responsible in 4.6% and FMR1 premutation in 2.4% of premature ovarian insufficiency cases, while the association of premature ovarian insufficiency-related genes was found very subtle. Novel variants in NR5A1, PDPK1, and POF1B may necessitate further evaluation for their association with premature ovarian insufficiency via functional studies.

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Keywords : Premature ovarian insufficiency, Gene, FMR1, Premutation, Menopause