AMH mutations with reduced in vitro bioactivity are related to premature ovarian insufficiency
Abstract
Could anti-Müllerian hormone (AMH) mutations be implicated in the development of idiopathic premature ovarian insufficiency (POI)? Three rare or unknown missense variants of the AMH gene were identified in a cohort of 55 POI patients; all three variants showed a drastically reduced in vitro bioactivity. Genetic factors are implicated in 5-15% of cases of POI. However, only a few genes have been shown to be involved in its development. AMH inhibits the recruitment of primordial follicles in the ovary and defective or absent AMH leads to premature depletion of the primordial follicle pool in AMH null mice. The whole coding sequence and the exon-intron junction of the AMH gene was sequenced in a cohort of 55 POI patients recruited over a period of 8 years. The studied variants were also sequenced in 197 ethnically matched controls. POI was defined as amenorrhea of more than 4 months with increased FSH before the age of 40. Patients with POI resulting from radio- or chemotherapy, surgery, chromosomal anomalies or FMR1 gene pre-mutation were excluded from the study. Recombinant human wild-type (wt) and mutated AMH proteins were produced in HEK293 T cells. KK-1 cells transfected with the AMH receptor type 2 (AMHR2) and a BMP responsi...Continue Reading
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Transcriptome Analysis of circRNA and mRNA in Theca Cells during Follicular Development in Chickens.
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