A team from the University Hospital of Santa Maria de Lleida, together with the Vall d"Hebron Research Institute, IRBLleida and professionals from the Vall d"Hebron University Hospital, has identified three people with a pathogenic variant linked to hereditary angioedema transmitted by the same sperm donor. This is the first documented case in the world of transmission of this pathology through an anonymous donor.
The research has been published in the scientific journal Frontiers in Immunology and stems from the case of a patient from Lleida who suffered recurrent episodes of swelling without response to conventional antiallergic treatment. Based on that condition, the specialists initiated the genetic study.
A patient from Lleida allowed to detect the genetic origin
The analysis identified in the patient the variant T328K of the F12 gene, an alteration that causes the disease in almost all cases of hereditary angioedema associated with that gene. The disorder causes recurrent episodes of swelling in the skin, the digestive system, or the respiratory tract.
Hereditary angioedema is a dominant genetic disease with incomplete penetrance. The form associated with the F12 gene affects men and women differently. In male carriers, the probability of developing symptoms is very low. In female carriers, however, the risk can be between 60% and 80%, often conditioned by hormonal factors.
"For clinicians, it is important to think about this disease when a patient presents recurrent episodes of swelling that do not respond to conventional antiallergic treatment, especially if there is a relationship with estrogens, as in the case of taking oral contraceptives or during pregnancy" - Mar Guilarte, Hospital Universitario Vall d"Hebron
The clinic contacted the sperm bank and two more cases emerged
After detecting the variant, the researchers contacted the corresponding fertility clinic, which coordinated the study with the sperm bank. The team confirmed that the donor was a heterozygous carrier of the T328K variant of the F12 gene.
After that verification, the clinic notified the situation to the women who had received semen from that donor. The tracing allowed locating two other carriers of the same genetic variant, who for now do not present symptoms of the disease.
"From a genetic point of view, this case is especially relevant because it demonstrates how a pathogenic variant can go unnoticed in an asymptomatic donor and be transmitted to several descendants" - Roger Colobran, VHIR
The researchers propose expanding screening in areas with more prevalence
The authors of the work maintain that in regions where this variant is more prevalent, such as the Iberian Peninsula, France, North Africa and Latin America, a targeted screening of the F12 gene could be considered. They also point out that future expansions of carrier studies could incorporate the pathogenic variant analyzed in this research.
Roger Colobran defended that assisted reproduction processes are safe and provide guarantees. He also recalled that in these procedures transmissible infectious pathologies and the most frequent genetic diseases, which can reach 300, are discarded. Even so, he warned that zero risk does not exist and maintained that assisted reproduction is genetically more guaranteeing than spontaneously pairing.
The study has been led by Lluís Marquès, Laura Batlle Masó, Eva Alcoceba, Sílvia Lara, Aina Aguiló, Johana Gil Serrano, Mar Guilarte and Roger Colobran. The signatories belong to the University Hospital of Santa Maria, the University Hospital Vall d"Hebron, IRBLleida and VHIR, in a work that opens the door to reviewing the scope of certain genetic screenings in assisted reproduction.