San Raffaele Hospital discovers new genetic mutation linked to sudden death

A new genetic mutation in the LMNA gene, associated with a severe form of cardiomyopathy that can cause sudden death, has been identified for the first time thanks to screening conducted in a small town in the Avellino area.

The discovery, published in the Journal of the American College of Cardiology: Heart Failure, is the result of a study by the IRCCS San Raffaele Hospital in Milan , conducted on 234 people originally from Caposele.

The mutation, called c.208del, was identified through a clinical genetic screening that began in 2022 and concluded in June 2024. 12.8% of the sample was found to carry the mutation: all present cardiac anomalies, often silent and undiagnosed, while 43% also show signs of neuromuscular involvement.

In some cases, early diagnosis has allowed for lifesaving interventions, such as implantable defibrillators or referral for transplant. Lamins, produced by the Lmna gene, are key structural proteins in the cell nucleus. Mutations in this gene give rise to so-called laminopathies, a heterogeneous group of diseases, often severe and potentially fatal.

The mutation was initially discovered in a young woman with mild arrhythmias but a long family history of sudden cardiac death. After receiving an implantable defibrillator, the patient survived a cardiac arrest. A second case, also with severe arrhythmias, confirmed the existence of familial transmission of the mutation.

Thanks to a digital genealogical reconstruction spanning over 12 generations and nearly 3,000 individuals, also carried out with the contribution of the Caposele community, it was possible to trace the hereditary spread of the mutation. Over 90% of the individuals traced participated in the screening, one of the most extensive ever conducted in a genetically isolated area of Southern Italy. An artificial intelligence algorithm helped predict potential carriers with 90% accuracy.