%0 Journal Article
%T Identification of a pathogenic mutation in ARPP21 in patients with amyotrophic lateral sclerosis.
%A Dols-Icardo O
%A Carbayo Á
%A Jericó I
%A Blasco-Martínez O
%A Álvarez-Sánchez E
%A López Pérez MA
%A Bernal S
%A Rodríguez-Santiago B
%A Cusco I
%A Turon-Sans J
%A Cabezas-Torres M
%A Caballero-Ávila M
%A Vesperinas A
%A Llansó L
%A Pagola-Lorz I
%A Torné L
%A Valle-Tamayo N
%A Muñoz L
%A Rubio-Guerra S
%A Illán-Gala I
%A Cortés-Vicente E
%A Gelpi E
%A Rojas-García R
%J J Neurol Neurosurg Psychiatry
%V 0
%N 0
%D 2024 Jul 2
%M 38960585
%F 13.654
%R 10.1136/jnnp-2024-333834
%X <B>OBJECTIVE: </B>Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing.<BR><B>METHODS: </B>We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data. We performed whole genome sequencing in a group of 12 patients with ALS (5 of them familial) from this unique area. We expanded the study to include affected family members and additional cases from a wider surrounding region.<BR><B>RESULTS: </B>We identified a shared missense mutation (c.1586C>T; p.Pro529Leu) in the cyclic AMP regulated phosphoprotein 21 (ARPP21) gene that encodes an RNA-binding protein, in a total of 10 patients with ALS from 7 unrelated families. No mutations were found in other ALS-causing genes.<BR><B>CONCLUSIONS: </B>While previous studies have dismissed a causal role of ARPP21 in ALS, our results strongly support ARPP21 as a novel ALS-causing gene.