Researchers from Sant Pau have discovered a new gene that causes ALS

Researchers 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, led by neurologist Dr. Ricardo Rojas-García, identified a new mutation in the ARPP21 gene. what may cause amyotrophic lateral sclerosis (ALS).

Specifically, it is a common mutation in the ARPP21 gene, which encodes an RNA-binding protein and It was detected in a total of 10 ALS patients from seven unrelated families in a region southeast of the autonomous community of La Rioja.

The investigation was launched following the discovery of an unusually high number of ALS cases in La Rioja, particularly in the south-eastern region of the autonomous community. The number of cases identified in the area, particularly familial cases, and the calculated minimum incidence significantly exceeded the number of cases expected during the study period, given the normal incidence data, which is usually between two and three cases per 100,000 inhabitants per year.

«We realized that there were a lot of patients from this area, from very nearby cities, which attracted a lot of attention.” explains Dr. Ricard Rojas-García, a researcher in the IR Neuromuscular Diseases Group and one of the study’s lead authors.

Between 5% and 10% of ALS cases have a family history of the disease, and in 30% of these cases, the underlying genetic cause cannot be identified after exhaustive testing of the genes known to be associated with the disease today. The aim of the Sant Pau researchers was to identify new genes associated with ALS in cases where genetic tests were negative, motivated by the significantly increased incidence of ALS in the area.

Scientists performed whole genome sequencing on a group of 12 patients with ALS (5 of them with a family history) from this single region. The study was expanded to include members of affected families and additional cases from a wider region. The mutation identified in ARPP21 has not been found in other ALS-causing genes. This finding strongly suggests that ARPP21 is a new ALS-causing gene.

Considering the average incidence of ALS of 1.4-2.47 cases/100,000 persons/year, the expected number of cases was calculated to be 0.44-0.77 per year in this area, which is equivalent to 5-10 patients during the study period (2009-2022). As for familial ALS cases, with an incidence of 5-10%, the expected number of cases in this area would be 0.02-0.08 cases per year, or one new case every 12.5-50 years.

However, between 2009 and 2022, 15 patients from the study area who met the diagnostic criteria for ALS were seen in Sant Pau. 7 of the 15 (46.6%) had a family history of ALS and were considered possible familial cases. Known mutations causing the disease were excluded using exome sequencing or a specific gene panel.

“This mutation will not only help to more accurately diagnose ALS, but alsoNo, it also opens the door to research into new personalized treatments and studying the function of this protein in disease.“,” adds Dr. Oriol Dols-Icardo, researcher in the Dementia and Memory Neurobiology Group at IR Sant Pau and the first signatory of the study.

Dols-Icardo believes these findings could open up new avenues for diagnosing and treating ALS. The identification of ARPP21 as the causative gene highlights the importance of further studies in specific geographic areas to discover new genetic factors.

Although the discovery was made in a specific region of Spain, the researchers believe it could have global implications. “This opens the door for other research groups around the world to look at their databases and patients to see if this mutation is present elsewhere,” they explain.

The discovery of a new gene associated with ALS will not only allow for improved diagnosis and genetic counseling for affected families, but will also open up new avenues for research into the function of this particular protein and its relationship to the disease.

This achievement highlights the importance of genetic research in understanding and treating rare diseases and underscores the need to continue studying the genetic causes of ALS to develop more effective treatments in the future.