ATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure

Título traducido de la contribución: Mutaciones pérdida de función en ATG7 y ATG9A contribuyen con la disfunción en la autofagia y conducen a POI

Clémence Delcour, Larbi Amazit, Liliana C Patino, Françoise Magnin, Jérôme Fagart, Brigitte Delemer, Jacques Young, Paul Laissue, Nadine Binart, Isabelle Beau

Producción científica: Contribución a una revistaArtículo de Investigaciónrevisión exhaustiva

60 Citas (Scopus)

Resumen

Purpose
Primary ovarian insufficiency (POI) is a frequent disorder that affects ~1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone (FSH), leads to infertility. Although various etiological factors have been described, including chromosomal abnormalities and gene variants, most cases remain idiopathic. The aim of the present study was to identify and validate functionally new sequence variants in ATG (autophagy-related genes) leading to POI.

Methods
We have reanalyzed, in silico, the exome sequencing data from a previously reported work performed in 69 unrelated POI women. Functional experiments using a classical hallmark of autophagy, the microtubule-associated protein 1 light chain 3β (LC3), were then used to link these genes to this lysosomal degradation pathway.

Results
We venture a functional link between ATG7 and ATG9A variants and POI. We demonstrated that variant ATG7 and ATG9A led to a decrease in autophagosome biosynthesis and consequently to an impairment of autophagy, a key biological process implicated in the preservation of the primordial follicles forming the ovarian reserve.

Conclusion
Our results unveil that impaired autophagy is a novel pathophysiological mechanism involved in human POI.
Título traducido de la contribuciónMutaciones pérdida de función en ATG7 y ATG9A contribuyen con la disfunción en la autofagia y conducen a POI
Idioma originalInglés
Número de artículo21
Páginas (desde-hasta)930–938
Número de páginas8
PublicaciónGenetics in Medicine
Volumen21
N.º4
DOI
EstadoPublicada - abr. 17 2019

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