Whole-genome and whole-exome sequencing of Mayer-Rokitansky-Küster-Hauser syndrome–discordant monozygotic twins

The absence of validated postzygotic mutations challenges coding variants as primary MRKHS drivers. Findings implicate Müllerian-restricted somatic mosaicism or epigenetic dysregulation (e.g., WNT4/LHX1 methylation) during embryogenesis, undetectable in peripheral blood. This underscores limitations of blood-based genomics and highlights the need for non-invasive biomarkers (e.g., cfDNA methylation) and prenatal environmental risk mitigation (e.g., endocrine disruptor avoidance). The study advocates integrating tissue-specific multi-omics and patient derived organoids to resolve MRKHS mechanisms, guiding fertility preservation and personalized reproductive interventions.