December 10, 2025

expert reaction to sperm donor passing on TP53 mutation

Scientists comment on a sperm donor carrying a cancer causing gene mutation used to conceive children.

Prof Allan Pacey, Professor of Andrology at the University of Manchester, said:

“This is a very tragic situation, and my heart goes out to everyone affected, including the donor who donated in good faith and was unaware that he had developed this mutation in his germline (the cells that make sperm).

“Unfortunately, this mutation would not have been detected by the screening tests that he underwent when he applied to be a donor. Moreover, we only screen for common genetic conditions either by an analysis of his family medical history or through specific blood tests. It is worth noting that for every 100 men who apply to be a sperm donor, only 2 or 3 will be eventually accepted. So, there is a danger that the more screening we do, the fewer donors we will have.

“What this case does highlight is the need to consider how often donor sperm can be used in treatment and how many children can be born from a single donor. At the moment, although countries have their own national limits, there are no international laws or regulations. So, when a donor’s sperm is sold and distributed in multiple countries there is no way to regulate this at the moment.”

Prof Dorothy Bennett, Professor of Cell Biology, City St George’s, University of London (CSGUL), said:

“Now the mutation has been identified, it could readily be screened for, and no doubt all the children from this donor’s sperm are being or will be screened.  Anyway, if they have developed cancer by 20 years old, they are likely to have the mutation, sadly – Li-Fraumeni syndrome (LFS).  There is not much that can then be done for the person except very regular cancer screening. 

The TP53 gene encodes the p53 protein, which could be called the most important human tumour suppressor gene.  It is mutated or defective in over half of all human cancers.     I can explain how it works if that would be useful – but in brief p53 can induce either cell death or permanent arrest (cell senescence) in cells that have divided too many times (like cancer cells), or that have too much damage to their DNA.  Only one of our 2 copies of TP53 needs to be mutated to stop it working, because the “bad” copies of p53 protein interfere with the good ones.

The donor evidently did not have the mutation in all his cells.  This is called a somatic mutation.  It must have appeared during his own development, possibly within one of the precursor cells of the sperm, called “primordial germ cells”, or maybe even after birth, since not even all of his sperm are carrying the mutation.”

Prof Clare Turnbull, professor of cancer genetics at The Institute of Cancer Research, London, said:

“This represents a highly unfortunate coincidence of two exceptionally unusual events: that the donor’s sperm carry mutations for an extremely rare genetic condition affecting fewer than 1 in 10,000 people and that his sperm has been used in the conception of such an extraordinarily large number of children.

“Li Fraumeni syndrome is a devastating diagnosis to impart to a family.  There is a very high risk of cancer throughout the lifetime.  And, unlike most cancer genetic susceptibility syndromes we encounter in clinic such as Lynch syndrome or that caused by the BRCA-genes for which the cancers are adult-onset, inherited mutations (pathogenic variants) in TP53 are associated with a sizeable risk of childhood-onset cancers.

“The TP53 mutation (pathogenic variant) was not present throughout the donor’s body tissues, meaning he had not inherited it.  The mutation would appear to have arisen in the testes but to have multiplied rapidly to affect a sizeable proportion of the spermatozoa, which have then been used for donation.

“This would potentially appear to be a demonstration of selfish spermatogonial selection, whereby a mutation can give the spermatogonial cells a growth advantage, allowing them to outcompete normal spermatogonia.”

Prof Jackson C Kirkman-Brown, Theme Lead – Reproductive & Maternal Health, School of Medical Sciences, College of Medicine & Health, The University of Birmingham, said:

“Screening for something de-novo in testis will never work on blood. Each sperm in an ejaculate is slightly different so screening these is also not simple – though if a child is born with a condition the screening sperm approach can be used to tell if a risk like this exists.

“In the end the issue here is around family limits and extended un-monitored use. 

“ESHRE are currently in the final stages of drafting a position on international family limits in donation. This is expected to be released formally in spring and is hoped to guide international legislation.”

Peter Thompson, Chief Executive of the HFEA, said: 

“We can confirm that the Danish Patient Safety Authority has informed us that a very small number of UK women have been treated in Danish Fertility clinics with this sperm donor. We understand that they have been told about the donor by the Danish clinic at which they were treated. As the UK regulator, we only collect or hold information about treatment which takes place in the UK. As the treatment took place at Danish clinics, further enquiries should be directed to the competent authority in Denmark.”

Declared interests

Prof Allan Pacey: AAP is a member of the Cryos International External Scientific Advisory Committee, he also undertakes consultancy for Carrot Fertility, and in the last two years has delivered educational lectures for IBSA Institut Biochemique SA, and Mealis Group but all monies were paid to the University of Manchester. He is also the co-chair of the UKNEQAS Reproductive Sciences Advisory Committee, is a member of the Advisory Boards for the Progress Educational Trust (Charity Number 1139856) and the Science Media Centre (Charity Number 1140827) and Patron of the Fertility Alliance (Charity Number 1206323 (all unpaid). He is a member of the Guidelines Development Groups for the National Institute for Health and Care Excellence, and the World Health Organisation (again all unpaid). 

Prof Dorothy Bennett: “I can declare no conflict of interest.”

Prof Clare Turnbull: Professor Turnbull is a member of the National Screening Committee Research and Methodology Group

Prof Jackson C Kirkman-Brown: “Sitting on the ESHRE ethics committee”

For all other experts, no reply to our request for DOIs was received.