Presentation description

Primary Ovarian Insufficiency (POI) causes women to lose their oocytes, fertility, and reduce ovarian hormone production before the age of 40, with 70% of POI causation currently unknown. We hypothesize that POI could be potentially caused by genetic mutations in genes that are known or by novel genes. We utilized International Classification of Diseases codes, electronic medical records notes, and follicle stimulating hormone laboratory values from Utah health databases to identify POI patients. Subjects were recruited, consented, and completed saliva kits (n=57). Saliva was processed to extract deoxyribonucleic acid (DNA) from epithelial cells. DNA was subjected to whole genome sequencing and entered into the GEM AI program to identify specific POI mutations, rare mutations, and possible candidates. We reviewed GEM picked variants on the GNOMAD database to distinguish variant location, heterozygotes, homozygotes, and In-Silico predictors. We found recessive, pathogenic variants in two genes (MCM8 and FANCM) known to cause POI. In patient 1: stop-gain and missense single nucleotide variants (SNV) were found for MCM8. In patient 2: splice donor and frameshift SNV were found for MCM8. In patient 3: stop-gained and missense SNV were found for FANCM. We conclude that two SNV of gene MCM8 leads to primary amenorrhea and two SNV of gene FANCM leads to secondary amenorrhea. We are continuing our analysis to identify new gene variants and novel genes to further classify additional gene mutation variants for POI. Identifying known and novel POI variants could lead to early identification and prevention for POI.