The first three cases of a rare disease in children of the same sperm donor have been described in Catalonia

Catalan researchers have identified the first three cases in the world of a hereditary genetic disease in children conceived with a single anonymous sperm donor. Professionals from the Vall d'Hebron Research Institute (VHIR) and Vall d'Hebron University Hospital, in collaboration with the allergy department of the University Hospital of Santa Maria de Lleida and the Biomedical Research Institute (IRBLleida), have identified three cases of hereditary angioedema, a rare and serious blood disorder—causing swelling of the face, hands, feet, limbs, genitals, intestinal tract, or upper respiratory tract—in the children of three women who underwent assisted reproduction. The research, published in the journal Frontiers in Immunology,It began with the case of a patient with recurrent swelling in her face and other parts of her body, with no apparent cause and unresponsive to standard allergy treatments. After ruling out allergies, doctors suspected the woman might have a rare form of hereditary angioedema, a theory confirmed by genetic testing, which identified the T328K variant of the F12 gene, commonly associated with this condition. Since she was conceived using sperm from an anonymous donor, researchers contacted the relevant fertility clinic, which coordinated the study with the sperm bank. They confirmed that the donor was a heterozygous carrier of the T328K variant of the F12 gene. Following this confirmation, the clinic notified other women who had received sperm from the same donor, and researchers identified two more carriers of the same genetic variant who currently have no symptoms of the disease. "From a genetic point of view, this case is especially relevant because it demonstrates how a pathogenic variant can go undetected in an asymptomatic donor and be transmitted to several offspring," explains Roger Colobran, head of the translational immunology group at VHIR. The research team points out that this finding highlights the challenges posed to gamete donation programs by dominant genetic diseases—those that can develop with only one copy of the affected gene—and which manifest differently in individuals carrying the mutation. Colobran clarifies that assisted reproduction processes "are safe and reliable," and even notes that "genetically, it is safer than spontaneous mating." Thus, transmissible infectious diseases and the most common genetic diseases, which can number up to 300, are ruled out. Differences between men and women

Colobran adds that "zero risk does not exist," as many genetic diseases exist, and suggests that future carrier studies could include the pathogenic variant of the F12 gene. The authors believe that the results of this study suggest that targeted screening for the F12 gene could be considered in certain regions where this variant is more prevalent, such as the Iberian Peninsula, neighboring countries like France, and countries in North Africa and Latin America.

This disorder affects men and women differently. In male carriers, the probability of developing symptoms is very low, while in female carriers it can reach 60% or 80%, often influenced by hormonal factors. This makes it possible for completely asymptomatic men to transmit the genetic variant unknowingly. "It's important to consider this condition when a patient experiences recurrent episodes of swelling that don't respond to conventional allergy treatment, especially if there's a link to estrogen, such as when taking oral contraceptives or during pregnancy," emphasizes Dr. Mar Guilarte, an allergy specialist and educator at Vall d'Hebron University Hospital and a researcher in the systemic diseases group at VHIR. The study was led by researchers Lluís Marquès, Laura Batlle-Masó, Eva Alcoceba, Silvia Lara, Aina Aguiló, Johana Gil-Serrano, Mar Guilarte, and Roger Colobran, professionals from Santa Maria University Hospital, Vall d'Hebron University Hospital, and the Hebron Research Institute (VHIR).