Exome-Based Identification of Candidate Genes in Sporadic Adenomyosis Cases

<b>Background</b>: Adenomyosis is a benign uterine disorder defined by the invagination of ectopic endometrial-like tissue into the myometrium, causing heavy menstrual bleeding and pain. While its pathogenesis remains unclear, shared-symptomology with endometriosis suggests a common mechanism. Adenomyosis is often diagnosed after age 40 due to its complex presentation and the need for histopathological confirmation, underscoring the need for non-invasive markers. <b>Methods</b>: Ten unrelated women with histopathological diagnosis of adenomyosis were recruited. All recruits completed the WERF-EPHect questionnaire and were additionally questioned about any comorbidities. Genomic DNA isolated from peripheral blood was subjected to whole exome sequencing (WES) on Illumina NovaSeq 6000 and was analyzed using the Pairend NGS Cloud platform. Variants were filtered for MAF < 1% and were prioritized based on functional relevance and impact determined by <i>in silico</i> prediction tools. Variant selection adhered to stringent quality metrics to identify candidate variants associated with adenomyosis. <b>Results</b>: WES analysis did not reveal any variant common to the cohort. A total of eight pathogenic and two likely pathogenic novel variants were identified. Moreover, novel variants of p.(Val331Ile) in <i>EFHB</i> and p.(Phe14Val) in <i>MEIS1</i> were the most frequently shared genetic variants in the cohort. <b>Conclusions</b>: Our findings suggest novel candidate genes for adenomyosis that warrant validation and functional investigation in larger, independent cohorts.