Τομέας Υγείας - Μητέρας - ΠαιδιούLibrary of the School of Health Sciences
Ανι?χνευση μοριακω?ν διαταραχω?ν σε γυναι?κες με πρω?ιμη ωοθηκικη? ανεπα?ρκεια
Background: The etiology of premature ovarian insufficiency (POI) is
multifactorial and may include genetic and/or environmental factors.
Αim of the study: The aim of the study was to search for genetic defects in
genes related to the development and/or function of the ovary and are linked to
POI: FOXL2, BMP15, GDF9, FOXE1 and NOBOX.
Subjects and Methods: 38 subjects with onset of POI at an early age (mean age
17.4 ± 6.6 years) were included in the study. Bidirectional sequencing of the
coding region of FOXL2, FOXE1, BMP15, NOBOX and GDF9 genes was performed. Fifty
female subjects from the general Greek population served as controls for the
genes FOXL2, BMP15 and NOBOX, and seventy five for the gene FOXE1.
Results: In the FOXL2 gene, a novel, de novo, heterozygous deletion
(p.K150Rfs*121) was detected in one subject (2.6%). In the FOXE1 gene, a novel
aberrant alanine tract was detected with genotype 8/16 in two patients and
genotype 8/14 in one patient (normal genotypes: 14/14 or 16/16). Three more
patients with aberrant alanine tract were detected with genotypes 12/16, 15/16
and 14/17, respectively. In the control group one individual had a FOXE1
alanine tract with a genotype of 8/14. In the BMP15 gene, the mutation
p.Q115H/WT was detected in one subject, in none of our controls or the 1000 GP
population. The mutation p.A180T/WT of the BMP15 gene was detected in 2.6% of
the patients, 0% of our control group and 0.5% of the 1000 GP population. The
genotype c.-9C>G + p.N103S of the BMP15 gene was detected in homozygosity in
5.2% of the patients, 0% of our controls and 0.5% of the 1000 GP population (p:
0.075). All the identified variants in the NOBOX gene were classified as
polymorphisms. No missense variants were detected in the GDF9 gene.
Conclusions: Genetic variants in five genes were searched for in patients with
relatively early onset of ovarian insufficiency (mean age 17.4 ± 6.6 years).
The percentage of genetic variants identified, as possibly related, to the
phenotype in our patients with POI was much higher than previously reported
(44.7% vs. 7%). The existence of genetic aberrations in two genes in five
subjects with POI, possibly indicates digenic inheritance, a phenomenon already
described in other nosologic entities.
Premature ovarian insufficiency, ΝΟΒΟΧ, FOXL2, FOXE1, BMP15
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