Categories: Health

The discovery of a new gene that causes ALS sheds some light on the diagnosis and treatment of the disease.

Researchers from the Neuromuscular Diseases Group and the Dementia Neurobiology Group of the Sant Pau Research Institute and the Memory Unit of the Hospital of Sant Pau have identified a new gene associated with amyotrophic lateral sclerosis (ALS), marking a major milestone in understanding and treating the disease. The discovery was published in the journal Journal of Neurology, Neurosurgery and PsychiatryA study by neurologist Ricard Rojas-Garcia has identified a mutation in the ARPP21 gene that may be critical in the etiology of ALS. Specifically, it is a common mutation. (c.1586C>T; p.Pro529Leu) in the ARPP21 gene which encodes an RNA-binding protein and was found in a total of 10 ALS patients from 7 unrelated families in a region southeast of the autonomous community of La Rioja.

The number of cases detected in the area, especially family cases, and the calculated minimum incidence significantly exceeded the expected number of cases.

The investigation began after an unusually high number of ALS cases were detected in La Rioja, particularly in the southeastern region of the autonomous community. The number of cases detected in the area, especially family cases, and the calculated minimum incidence significantly exceeded the number of cases expected during the study period given the usual incidence data.which typically amounts to two to three cases per 100,000 inhabitants per year.

Target

Between 5 and 10 percent of ALS cases have a family history of the disease, and in 30 percent of these cases, an underlying genetic cause cannot be identified after exhaustive testing of known ALS-associated genes to date. 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 this small geographic region of Spain..

The aim of the Sant Pau researchers was to identify new genes associated with ALS in cases where genetic tests were negative.

In this regard, the scientists performed whole-genome sequencing of a group of 12 ALS patients (5 of them with a family history) from this unique 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 over the study period (2009-2022). Therefore, according to these data, The hospital notes that the expected number of cases in the area will be 0.02-0.08 cases per year, or one new case every 12.5-50 years.

Care

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

This mutation will not only help more accurately diagnose ALS, but will also open the door to research into new personalized treatments.

In this sense, Oriol Dols-Icardo, researcher in the Dementia and Memory Neurobiology Group at IR Sant Pau and first signatory to the studyexplains that the discovery of this mutation will not only help to more accurately diagnose ALS, but also opens the door to research into new personalized treatments and studying the function of this protein in the disease. In fact, he believes that these findings may 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.

The best diagnostics

Although this discovery was made in a specific region, 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. Furthermore, they stress that 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 highlights the need to continue to study the genetic causes of ALS to develop more effective treatments in the future.