RAN-Translation in fragile X associated Premature Ovarian Insufficiency (FXPOI) FMRpolyG as predictive tool?

Introduction Fragile X-associated primary ovarian insufficiency (FXPOI is characterized by oligo/amenorrhea and hypergondotropic hypogonadism. About 20% of women who carry an FMR1 premutation (PM) allele develop FXPOI. RAN translation of CGG repeats into a polyglycine-containing protein, FMRpolyG is proposed to cause FXPOI. FMRpolyG expression in granulosa cells (GCs) leads to perturbed ovarian function. However, FMRpolyG has not been discovered in human lymphocytes and GCs of FXPOI yet.

Methods Western blot (WB) was performed to detect the expression of FMRP and FMRpolyG in patient´s lymphocytes and GCs.

Results Firstly, we could detect FMRP both in human lymphocytes and GCs. FMRP shows a clear protein pattern with a major band at 80 kDa, and 3-4 minor bands as shown in HEK293 and COV434 cell lines. FMRP expressed the greater amount and was determined for the first time in granulosa cells with WB. We continued to investigate the expression of FMRpolyG in GCs of permutation patients. FMRpolyG is hard to detect in granulosa cells of patient samples due to a lower number of cells. FMRpolyG may bind to another ubiquitination protein like HSP-70; therefore we are continuing to characterize FMRpolyG by performing immunoprecipitation and WB.

Conclusion We showed for the first time the different expression patterns of FMRP in human lymphocytes compared to the female germline. We aim to study the step by step development of the disease and to identify FMRpolyG as an early marker of progression, have been not conclusive. Experiments on more patients are in progress to address this point.

Publication History

Article published online:
07 October 2020