TY - JOUR
T1 - The Potential Synergic Effect of a Complex Pattern of Multiple Inherited Genetic Variants as a Pathogenic Factor for Ovarian Dysgenesis
T2 - A Case Report
AU - Cattoni, Alessandro
AU - Spano, Alice
AU - Tulone, Anna
AU - Boneschi, Annalisa
AU - Masera, Nicoletta
AU - Maitz, Silvia
AU - Di Blasio, Anna Maria
AU - Persani, Luca
AU - Guizzardi, Fabiana
AU - Rossetti, Raffaella
N1 - Funding Information:
Funding. This work has been partially supported by Italian Ministry of Health ?Ricerca Finalizzata' grant (GR-2011-02351636, BIOEFFECT) and by IRCCS Istituto Auxologico Italiano (RICCOR).
Publisher Copyright:
© Copyright © 2020 Cattoni, Spano, Tulone, Boneschi, Masera, Maitz, Di Blasio, Persani, Guizzardi and Rossetti.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/9/25
Y1 - 2020/9/25
N2 - Non-syndromic primary ovarian insufficiency due to ovarian dysgenesis in 46,XX patients is an uncommon finding in the general population, even though several monogenic variants have been reported as causative factors. Here, we describe a 15-year-old patient diagnosed with gonadal dysgenesis possibly due to the interaction of three potentially pathogenic variants of genes involved in ovarian maturation, namely factor in the germline alpha (FIGLA), newborn ovary homeobox-encoding (NOBOX) and nuclear receptor subfamily 5 group A member 1 (NR5A1). We also describe a different degree of residual ovarian function within the proband's family, whose female members carry one to three demonstrated variations in the aforementioned genes in a clinical spectrum potentially dependent on the number of alleles involved. Our results support the hypothesis that the severity of the clinical picture of the proband, resulting in complete ovarian dysgenesis, may be due to a synergic detrimental effect of inherited genetic variants.
AB - Non-syndromic primary ovarian insufficiency due to ovarian dysgenesis in 46,XX patients is an uncommon finding in the general population, even though several monogenic variants have been reported as causative factors. Here, we describe a 15-year-old patient diagnosed with gonadal dysgenesis possibly due to the interaction of three potentially pathogenic variants of genes involved in ovarian maturation, namely factor in the germline alpha (FIGLA), newborn ovary homeobox-encoding (NOBOX) and nuclear receptor subfamily 5 group A member 1 (NR5A1). We also describe a different degree of residual ovarian function within the proband's family, whose female members carry one to three demonstrated variations in the aforementioned genes in a clinical spectrum potentially dependent on the number of alleles involved. Our results support the hypothesis that the severity of the clinical picture of the proband, resulting in complete ovarian dysgenesis, may be due to a synergic detrimental effect of inherited genetic variants.
KW - antimullerian hormone (AMH)
KW - fertility
KW - FIGLA gene
KW - gene variants
KW - gonadal dysgenesis (GD)
KW - NOBOX gene
KW - NR5A1 gene
KW - primary ovarian insufficiency (POI)
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U2 - 10.3389/fendo.2020.540683
DO - 10.3389/fendo.2020.540683
M3 - Article
AN - SCOPUS:85092319245
VL - 11
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
SN - 1664-2392
M1 - 540683
ER -