Researchers from IRBLleida and the Vall d'Hebron Institute of Research identify several cases of a rare disease transmitted by a sperm donor

Professionals from the Allergy service of the Santa Maria University Hospital in Lleida, in collaboration with the Vall de Hebrón Institute for Research (VHIR), the Institute for Biomedical Research of Lleida (IRBLleida) and professionals from Vall de Hebrón University Hospital, have described the world's first documented case of transmission of hereditary angioedema associated with the F12 gene through an anonymous sperm donor.

The study, published in the scientific journal Frontiers in Immunology, highlights the identification of several cases carrying the same genetic variant, all conceived using assisted reproductive techniques from a single donor.

The research began with the case of a patient who experienced recurrent episodes of swelling (angioedema) on her face and other parts of her body for no apparent reason and who did not respond to standard anti-allergic treatments. Tests ruled out an allergic origin and pointed to a rare form of hereditary angioedema. Genetic analysis identified the T328K variant of the F12 gene, associated with a bradykinin-mediated form of the disease. This variant is a recurrent variant that causes the disease in almost 100% of cases of F12-associated hereditary angioedema.

In the follow-up study, the same variant was detected in other individuals conceived using semen from the same donor, whilst it was not present in the maternal lineage analysed. This finding led to the suspicion that the mutation might have originated from the donor.

The researchers contacted the relevant fertility clinic, which coordinated the study with the sperm bank. Genetic testing confirmed that the donor was a heterozygous carrier of the T328K variant of the F12 gene.

Following this confirmation, the clinic initiated a process to notify the women who had used sperm from this donor.

This procedure enabled the identification of other carriers of the same genetic variant, some of whom currently show no clinical symptoms.

A rare disease with different manifestations depending on sex

Hereditary angioedema is a rare genetic disorder that causes recurrent episodes of swelling of the skin, the digestive tract or the airways. In some cases, it can become potentially serious.

It is an autosomal dominant genetic disorder; therefore, having just one copy of the affected gene is sufficient to develop the condition. However, it has incomplete penetrance and variable expressivity, meaning that the onset and severity of symptoms are not the same in all individuals carrying the mutation.

The form associated with the F12 gene has a distinctive feature: it affects men and women differently. In male carriers, the likelihood of developing symptoms is very low, whereas in female carriers it can reach 60-80%, often influenced by hormonal factors. This means that completely asymptomatic men can pass on the genetic variant without realising it.

Implications for assisted reproduction

The researchers highlight that this case highlights the challenges posed by dominant genetic disorders with incomplete penetrance in gamete donation programmes. Currently, genetic screening of donors focuses mainly on infectious diseases and certain common recessive disorders. According to the authors, the results of this study suggest that, in certain regions where this variant is more prevalent, targeted screening for the F12 gene could be considered.

The study was led by researchers Lluís Marquès, Laura Batlle-Masó, Eva Alcoceba, Sílvia Lara, Aina Aguiló, Johana Gil-Serrano, Mar Guilarte and Roger Colobran, professionals from Santa Maria University Hospital, Vall d'Hebron University Hospital, the Institute for Biomedical Research of Lleida (IRBLleida) and the Vall d'Hebron Research Institute (VHIR).

Article: Marquès L, Batlle-Masó L, Alcoceba E, Lara S, Aguiló-Cucurull A, Gil-Serrano J, Guilarte M and Colobran R (2026) Transmission of F12-related hereditary angioedema through a sperm donor. Front. Immunol. 17:1799395. doi: 10.3389/fimmu.2026.1799395

Text: Comunicación HUAV / GSS