A recent study published in Genome Biology and Evolution sheds light on the intricate relationship between parental age and rare congenital disorders, challenging previous assumptions about the role of paternal age in genetic mutations.
While it has been widely recognized that advanced paternal age is associated with an increased risk of certain congenital disorders, including bone and heart malformations, neurodevelopmental disorders, schizophrenia, and autism, the study reveals a more nuanced understanding of this connection. Contrary to previous beliefs, the link between paternal age and specific pathogenic mutations is not uniform, and some mutations may even arise in the father’s testis before sexual maturity.
The study highlights the significance of driver mutations, which have the potential to cause congenital disorders and are disproportionately prevalent in the male germline, particularly in older men. Despite their prevalence and potential pathogenic effects, the origin and prevalence of these mutations remain poorly understood.
To investigate this further, researchers collected sperm samples from anonymous donors across a wide age range and examined the variant frequency for genetic mutations associated with fibroblast growth factor receptor 3 (FGFR3) variants—a protein implicated in various congenital disorders.
Their findings revealed that certain FGFR3 variants, such as those linked to achondroplasia and Thanatophoric dysplasia, exhibit an increased frequency with paternal age. However, many other FGFR3 variants showed no correlation with paternal age, challenging the notion that advanced paternal age is universally associated with an elevated risk of all congenital disorders.
Lead author Irene Tiemann-Boege emphasizes that while older fathers indeed face a higher risk of transmitting specific pathogenic mutations, young fathers also carry a risk, challenging the assumption that only advanced paternal age poses genetic risks.
Overall, the study underscores the complexity of the relationship between parental age and congenital disorders and highlights the need for further research to elucidate the underlying mechanisms driving these associations.
