ASHG 2021: Male infertility may be related to these new mutations

The American Society of Human Genetics (ASHG) 2021 annual meeting was held online last week

In this study, researchers from multiple countries sequenced the exomes of 185 men with severe oligospermia or azoospermia, and compared their protein coding sequences with those of their parents without the disease.

Miguel Xavier, a postdoctoral researcher at the Institute of Biological Sciences at Newcastle University, said: "In the past, male infertility was studied under a recessive genetic model, but according to this method, a large part of the cases still cannot find the cause

With this in mind, the research team began to look for de novo mutations from infertile male participants, that is, mutations that were not inherited from their parents

They identified 192 rare new mutations in affected men

The researchers report that this includes 21 missense mutations, 4 frameshift mutations, a small number of in-frame insertions or deletions, and 1 premature termination mutation

"We did not find other genetic abnormalities in these male patients, which seems to indicate that the new mutation is the genetic cause of infertility in these men," Xavier added, noting that these mutations seem to have a dominant effect on infertility

In follow-up studies, they also found 5 rare missense mutations affecting the RBM5 gene in a cohort of 2,279 infertile patients, but no such mutations were found in a cohort of 5,784 fertile men

Xavier pointed out that more research is needed to discover potential factors that lead to infertility in a larger group of participants

"Hopefully in the near future, we will be able to determine more genetic causes of infertility and develop methods to treat these patients’ infertility

Currently, this result has been published on the BioRxiv preprint website, entitled "A de novo paradigm for male infertility"