In-Frame Variants in Gene Cause Premature Ovarian Insufficiency.

Front Genet

Institute of Reproduction and Stem Cell Engineering, Central South University, Changsha, China.

Published: November 2019

Premature ovarian insufficiency (POI) is a severe clinical syndrome defined by ovarian dysfunction in women less than 40 years old who generally manifest with infertility, menstrual disturbance, elevated gonadotrophins, and low estradiol levels. is considered a genetic aetiology of POI, which facilitates entry of REC8 into the nucleus of a cell and plays an essential role in gametogenesis. At present, only six truncated variants associated with POI have been reported; there have been no reports of an in-frame variant of causing POI. In this study, two novel homozygous in-frame variants (c.877_885del, p.293_295del; c.891_893dupTGA, p.297_298insAsp) in were identified in two sisters with POI from a five-generation consanguineous Han Chinese family. To evaluate the effects of these two variants, we performed fluorescence localization and co-immunoprecipitation analyses using cell model. The two variants were shown to be pathogenic, as neither STAG3 nor REC8 entered nuclei, and interactions between mutant STAG3 and REC8 or SMC1A were absent. To the best of our knowledge, this is the first report on in-frame variants of that cause POI. This finding extends the spectrum of variants in and sheds new light on the genetic origins of POI.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868891PMC
http://dx.doi.org/10.3389/fgene.2019.01016DOI Listing

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