The revelation that donor sperm from Denmark carrying a serious pathogenic mutation in the tumor suppressor gene TP53, which increases the risk of cancer, was used for years for the birth of nearly 200 children in 14 countries—among them 18 in Greece—has sounded a global alarm.

With 11 families in our country currently living in anxiety and the investigation continuing, the competent authorities are trying to fully map the cases. As made known by the Professor of Hematology-Oncology at the Children’s Hospital “Agia Sofia,” Antonis Kattamis, according to the data so far, one child born from the donor’s genetic material has lost his life, while his sibling is suffering from cancer. The couple had three children using sperm from the Danish donor.

According to expert scientists, the case reveals that even strict protocols cannot completely eliminate risk. At the same time, the discussion about the number of children that may be born from a single donor is reopening, underscoring the need for stable, international rules that will ensure the greatest possible safety for children and parents.

On this serious issue, which has caused intense concern among families and the scientific community throughout Europe, the Athens–Macedonian News Agency (ANA-MPA) turned to the Emeritus Professor of Genetics at the Medical School of the National and Kapodistrian University of Athens, Jan Traeger-Synodinos, former director of the Medical Genetics Laboratory and regular member of the National Authority of Medically Assisted Reproduction (2021–2024), in order to clarify the real risks, the limits of genetic screening, and the gaps highlighted by the case of the donor with the TP53 mutation.

The professor explains what applies today in Greece regarding donor screening and the number of uses of gametes, as well as why, despite protocols, the risk of the appearance of a rare genetic disease can never be fully excluded.

“First of all, this case is extremely distressing for all the families that have been affected. At the same time, it highlights some of the risks of in vitro fertilization (IVF), which are related:

a) to the transmission of genetic diseases to offspring and
b) to how many times a donor’s gametic cells are allowed to be used,” notes Ms. Traeger-Synodinos.

What the variant in the TP53 gene means

“The variant in this specific oncogene is characterized as ‘pathogenic’ based on the criteria of the ACMG (American College of Medical Genetics). The mutation arose spontaneously during the donor’s embryonic development and is not present in all of his cells (mosaicism). However, it is estimated that approximately 20% of his cells—including sperm cells—carry the variant. Consequently, any child resulting from an IVF procedure using an ‘affected’ sperm cell will inherit the variant in all of his or her cells, which entails a very high risk of developing many types of cancer, such as, for example, in Li-Fraumeni syndrome. Even the donor himself has an increased risk of developing cancer at some point in his life.”

When asked whether the mutation could have been detected preventively, Professor Jan Traeger-Synodinos answers: “The standard source of DNA for genetic testing is white blood cells from a whole blood sample. All diagnostic platforms are calibrated to detect variants at a level of around 50%, with a lower sensitivity threshold of about 30%. Therefore, routine DNA tests do not have the sensitivity to detect this specific TP53 variant.

On a practical level, such high sensitivity is not required—clinically significant mosaicisms are extremely rare. This particular donor constitutes an extremely unusual case, and it is not realistic to apply such highly specialized tests in everyday practice.”

Which genetic tests must be carried out on gamete donors

The required tests are determined by the applicable legal framework, although they are similar throughout Europe. They include at a minimum:

• clinical and psychological evaluation,
• exclusion of basic infections,
• genetic testing, which may be limited (e.g., in the United Kingdom only for cystic fibrosis) or more extensive.

In Greece, screening includes indicatively:

• carrier status for Mediterranean and sickle cell anemia,
• carrier status for cystic fibrosis (with ≥99% coverage of pathogenic variants),
• classical karyotype,
• carrier status for spinal muscular atrophy (SMN1 gene),
• carrier status for non-syndromic deafness (GJB2 gene, connexin),
• for female donors: carrier screening for fragile X syndrome (Fragile-X).

“The couple may choose more extensive genetic screening, but there always remains a small residual risk for extremely rare diseases,” Jan Traeger-Synodinos tells ANA-MPA.

She also notes that “most genetic diseases are transmitted as autosomal recessive, with a 25% risk when both parents are carriers (e.g., cystic fibrosis, Mediterranean anemia). Others are X-linked recessive (transmitted from a carrier mother to sons with a 50% risk). Autosomal dominant diseases usually cause disease in the adult carrier—therefore such a person would not be accepted as a donor.”

In Greece, the recommended molecular screening for autosomal recessive diseases significantly limits the occurrence of common severe genetic disorders in offspring. More extensive screening remains optional, explains the Emeritus Professor of Genetics at the Medical School of the National and Kapodistrian University of Athens.

Maximum number of offspring per donor

Asked about the number of uses of gametes from a single donor, Professor Jan Traeger-Synodinos emphasizes that “the aim is to minimize the risk of accidental consanguinity in the future.” She adds that ESHRE (European Society of Human Reproduction and Embryology) is developing new international guidelines regarding the maximum number of offspring per donor.

In Greece, she notes, legislation has been in force since 2005 (with recent amendments), which stipulates that the gametic cells of each donor may be used in up to 12 families in total.

Since 2022, a National Registry of Gamete Donors has also been operating, contributing to monitoring:

• the number of offspring per donor,
• the risk of using gametes that may later be associated with a genetic disease.

“This particular case is a reminder that there is always a risk of the appearance of genetic disorders—both in natural conception and in assisted reproduction.

Couples must be adequately informed by specialist geneticists and have at their disposal options that reduce this risk.

Moreover, it becomes clear that all countries must strictly apply limits on the number of offspring per donor,” concludes the Emeritus Professor of Genetics at the Medical School of the National and Kapodistrian University of Athens, Jan Traeger-Synodinos.