Novel Variants in MCM8 Associated with Primary Ovarian Insufficiency, Short Stature, and Congenital Anomalies of the Kidneys in a Patient from Georgia: A Case Report

Abstract

Primary ovarian insufficiency (POI) is a major cause of female infertility, resulting from the premature loss of ovarian function. Recently, pathogenic variants in the minichromosome maintenance (MCM) complex component 8 (MCM8) have been associated with POI. We report a case of a 13-year-old female from Georgia presenting with POI, short stature, and congenital kidney anomalies, in whom whole exome sequencing (WES) identified two novel heterozygous variants: a frameshift variant, c.278_281del, p.(Ile93Argfs*22), and a missense variant, c.703T>C, p.(Cys235Arg). The patient’s clinical presentation, which includes previously unreported kidney anomalies, and the identification of novel variants expand the phenotypic and molecular spectrum of MCM8-related POI. The presented case also highlights the critical role of WES in diagnosing unexplained POI, leading to early diagnosis and management. A literature review of existing MCM8 variants is also provided, emphasizing the necessity of additional functional studies to fully understand its role in ovarian function and related abnormalities.