They discover the gene that causes ALS after discovering a large number of cases in La Rioja Baja.

There were too many cases. In too small a space and too little time. A proportion that went beyond all statistical parameters expected for the population of a given territory. From that moment on, a study began that ended, although still in the preliminary stage, with the identification of the gene underlying one of the most devastating diseases. This disease is amyotrophic lateral sclerosis, better known as ALS: a degenerative, incurable and terrible disease that little by little leaves the patient without treatment and control over his body. And this is the region of La Rioja Baja.

The study led to the discovery of a genetic mutation present in people from seven unrelated families living in Quel, Autol, Cornago and Aguilar, as well as in one municipality in Navarre and another in Soria.

The study was carried out at the Sant Pau Hospital in Barcelona. There, as Dr. Ricard Rojas-García explains, they realized that in La Rioja, especially in the southeastern region of the autonomous community, there was “an unusually high number of ALS cases.” The incidence is much higher than usual, and is usually between two and three cases per 100,000 inhabitants per year. “We realized that there were many patients from this area, from very nearby towns, which attracted a lot of attention.”

Hereditary cases

According to the study, published yesterday in the specialized journal “Journal of Neurology, Neurosurgery and Psychiatry”, in the study area, between 2009 and 2022, there were an average of 43,433 people, of whom 31,324 were over 18 years old. According to the known incidence in this area, one would expect (in the period 2009-2022, the purpose of the study) a minimum of 5 and a maximum of 10 cases of ALS. However, in La Rioja Baja there were 15.

But what was further away than expected was the frequency of “hereditary” cases. That is, those with a family history. In the population under consideration, it was expected that at worst a new patient of this type would appear every twelve and a half years, or every fifty if “lucky”, still within the normal range. But in the thirteen years from 2009 to 2022, seven cases of this type appeared in this area of ​​La Rioja Baja.

It was therefore necessary to look for a genetic cause that could explain this hereditary incidence. Scientists from the Neuromuscular Diseases Group and the Dementia Neurobiology Group of the Sant Pau Research Institute (IR Sant Pau) and the Memory Unit of the Sant Pau Hospital carried out whole genome sequencing on a group of 12 ALS patients (5 of them with a family history) from this area. The study was then expanded to include members of affected families and additional cases from a wider region.

Known mutations causing the disease were excluded, leading to a mutation in the ARPP21 gene, which was found in a total of 10 ALS patients from 7 unrelated families. The seven families live in four cities in La Rioja: Quel, Autol, Cornago and Aguilar, as well as other cities in Navarra and Soria.

Global implications

Although this discovery was made in a specific region, such as La Rioja Baja, the researchers believe it could have global implications. “This opens the possibility for other research groups around the world to look at their databases and patients to see if this mutation is present elsewhere,” the study authors explain.

“This mutation will not only help to more accurately diagnose ALS, but will also open the door to research into new personalized treatments and to study the function of this protein in the disease,” adds Dr. Oriol Dols-Icardo, the first signatory of the study.