Fanconi Anaemia (FA) is a rare disorder with autosomal recessive inheritance, impacting multiple bodily systems. FA involves progressive bone marrow failure, cancer susceptibility, limb defects, reduced fertility in females and complete sterility in males. The condition is a result of mutations in any of the 22 FANC genes that are part of the FA pathway, which repairs inter-strand crosslinks that are a consequence of spontaneous DNA damage in somatic cells.
FANCM is a crucial gene in the FA pathway which acts as a DNA translocase and has been shown to maintain genomic stability. Loss of FANCM correlates with reduced fertility in humans and mice, affecting normal gametogenesis. A mouse model bred until the F5 generation showed a significant decline in fertility among Fancm-/- mice, indicating heritability. Genomic instability analysis revealed increased de novo and inherited structural variants (SVs) in Fancm-/- mice compared to a control population, possibly impacting gamete development or fertilisation.
Enhanced comprehension of the genetic mechanisms underlying reduced fertility is of interest to the FA community. Given the improvements in health outcomes and life expectancy, there is a growing interest in exploring fertility options for individuals with FA. Exploring genomic instability's role and identifying SV locations within the genome could deepen our understanding of FA pathway genes and their involvement in gametogenesis. This research may also contribute to a broader understanding of unexplained infertility beyond FA.