Understanding the novelMCM8gene mutation: primary ovarian insufficiency and uterine hypoplasia in siblings

Abstract

This case report elucidates a scenario involving two sibling sisters born out of consanguineous marriage—one initially presenting with lower respiratory infection, concurrently exhibiting short stature and primary amenorrhoea. Investigation into the primary amenorrhoea unveiled hypergonadotropic hypogonadism, confirmed by the absence of ovaries and a hypoplastic uterus on pelvic MRI. Genetic analysis via whole exome sequencing identified a homozygous variant NM_001282717.2: c.808C>T in the MCM8 gene, located on exon 8 of chromosome 20, inherited in an autosomal recessive manner. The scarcity of primary ovarian insufficiency cases linked toMCM8highlights the necessity of thoroughly investigating the genetic and clinical consequences of such variants.