Related Experiment Video
Updated: Mar 6, 2026
Z-Scores for Assessing Ovarian Reserve in Young Patients Undergoing Fertility Preservation
Published on: October 25, 2024
A novel homozygous growth differentiation factor 9 variant associated with premature ovarian insufficiency: A case
Behzad Haj Mohammad Hassani1, Niloofar Ghasemi1, Kianoosh Malekzadeh1,2
1Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Insights
This study identified a novel homozygous GDF9 variant causing premature ovarian insufficiency (POI) in two sisters. Heterozygous variants in the family did not cause POI, suggesting biallelic GDF9 variants are crucial for disease development.
Area of Science:
- Genetics
- Reproductive Biology
- Endocrinology
Background:
- Premature ovarian insufficiency (POI) is characterized by diminished ovarian function.
- Genetic variants, including those in Growth Differentiation Factor 9 (GDF9), are linked to POI.
- GDF9 is vital for ovarian follicular development.
Background:
Premature ovarian insufficiency (POI) is a condition marked by reduced ovarian function. The variants in several genes have been identified in association with POI. Growth differentiation factor 9 (GDF9) is one of these genes, which encodes a secreted protein with an essential role in follicular development.
Case Presentation:
Our study investigates the cause of early secondary amenorrhea in 2 affected sisters with POI from a consanguineous Iranian family. Exome sequencing identified a novel homozygous GDF9 variant (c.275T C; p.Leu92Pro) in the probands. Based on family segregation analysis, the variant was detected in a heterozygous state in the parents of the affected sisters and their grandmother. Notably, neither the mother nor the grandmother showed symptoms of the disease. Bioinformatics analysis and protein structural alteration due to the substitution of leucine with proline also supported the deleterious potential impact of this variant.
Conclusion:
In summary, our findings highlight the role of GDF9 biallelic variants in the etiology of POI and suggest a more cautious interpretation of heterozygous variants in the context of disease.
More Related Videos
Related Concept Videos
02:07Oogenesis
01:22Oogenesis
Each primary oocyte is surrounded by a layer of pre-granulosa cells, forming what is...
01:20Folliculogenesis
01:33Pleiotropy
01:24Gonadal and Placental Hormones
In males, testosterone is the primary gonadal androgen. It plays a central role in the maturation of male reproductive organs — the penis and testes. Additionally, testosterone is instrumental in the development of secondary sexual characteristics — a deep voice as well as facial and pubic hair...
01:30Hormonal Control of the Ovarian Cycle
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...