Identification of Novel Nucleotide Changes in INHBB Gene by Mutation Screening in Females with Ovarian Dysgenesis: A Case Report

Pooja  Chauhan; Anjali  Rani; Amit Kumar  Rai

doi:10.18502/jri.v22i4.7656

Pooja Chauhan Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, Varanasi, India
Anjali Rani Department of Obstetrics and Gynaecology, Institute of Medical Science, Banaras Hindu University, Varanasi, India
Amit Kumar Rai Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, Varanasi, India

DOI: https://doi.org/10.18502/jri.v22i4.7656

Keywords: Amenorrhea, Follicle stimulating hormone, Gonadal dysgenesis, Inhibins, Luteinizing hormone, Mutation.

Abstract

Background: Inhibin and activin regulate the follicle stimulating hormone level by their antagonistic actions and thus have been considered as strong candidate genes in the etiology of ovarian dysgenesis. In the present study, two cases of primary amenorrhea with poorly developed secondary sexual characteristics were reported. The purpose of the study was to identify mutations in candidate gene.

Case Presentation: In this paper, clinical, genetic, biochemical, and molecular findings in female patients with primary amenorrhea were reported. Whole blood culture and G-banding for karyotyping, sequencing, and in silico analysis were performed following the standard protocol. Both cases were cytogenetically characterized as normal females with 46,XX, chromosome constitution. Hormonal assay revealed high level of follicle stimulating hormone and luteinizing hormone. DNA sequence analysis of inhibin identified two novel heterozygous missense mutations of c.975T>A and c.1156G>A which were translated into p.I310N and p.D386N, respectively. These identified positions were highly conserved across species during evolution. In silico prediction tools, intramolecular hydrogen bonding pattern and hydrophobicity analysis, revealed deleterious effect of p.I310N and neutral effect of p.D386N mutation.

Conclusion: Our observation suggested that identified novel mutation in the first case might be the reason for ovarian dysgenesis and provides additional support to the previously reported genotype-phenotype correlations.