Identification of a pathogenic mutation in ARPP21 in patients with amyotrophic lateral sclerosis
Por:
Dols-Icardo, O, Carbayo, A, Jericó, I, Blasco-Martínez, O, Alvarez-Sánchez, E, Pérez, MAL, Bernal, S, Rodríguez-Santiago, B, Cusco, I, Turon-Sans, J, Cabezas-Torres, M, Caballero-Avila, M, Vesperinas, A, Llansó, L, Pagola-Lorz, I, Torné, L, Valle-Tamayo, N, Muñoz, L, Rubio-Guerra, S, Illán-Gala, I, Cortés-Vicente, E, Gelpi, E, Rojas-García, R
Publicada:
1 feb 2025
Ahead of Print:
1 jul 2024
Resumen:
Background and objective 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. Methods 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. Results 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. Conclusions While previous studies have dismissed a causal role of ARPP21 in ALS, our results strongly support ARPP21 as a novel ALS-causing gene.
Filiaciones:
Dols-Icardo, O:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Carbayo, A:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, Motor Neuron Dis Clin,Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona, Spain
Jericó, I:
Hosp Univ Navarra, Dept Neurol, Neuromuscular & Motor Neuron Dis Res Grp, Pamplona, Spain
Hlth Res Inst Navarra IDISNA, Pamplona, Spain
Blasco-Martínez, O:
Hosp San Pedro, Dept Neurol, Logrono, La Rioja, Spain
Alvarez-Sánchez, E:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Pérez, MAL:
Hosp San Pedro, Dept Neurol, Logrono, La Rioja, Spain
Bernal, S:
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St PAU, Genet Dept, Barcelona, Spain
Rodríguez-Santiago, B:
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St PAU, Genet Dept, Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Genome Instabil & DNA Repair Grp, Barcelona, Spain
Cusco, I:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St PAU, Genet Dept, Barcelona, Spain
Turon-Sans, J:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, Motor Neuron Dis Clin,Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona, Spain
Cabezas-Torres, M:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, Motor Neuron Dis Clin,Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Caballero-Avila, M:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, Motor Neuron Dis Clin,Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona, Spain
Vesperinas, A:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, Motor Neuron Dis Clin,Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona, Spain
Llansó, L:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, Motor Neuron Dis Clin,Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona, Spain
Pagola-Lorz, I:
Hosp Univ Navarra, Dept Neurol, Neuromuscular & Motor Neuron Dis Res Grp, Pamplona, Spain
Hlth Res Inst Navarra IDISNA, Pamplona, Spain
Torné, L:
Hosp Univ Navarra, Dept Neurol, Neuromuscular & Motor Neuron Dis Res Grp, Pamplona, Spain
Hlth Res Inst Navarra IDISNA, Pamplona, Spain
Valle-Tamayo, N:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Muñoz, L:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Rubio-Guerra, S:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Illán-Gala, I:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Cortés-Vicente, E:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, Motor Neuron Dis Clin,Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona, Spain
Gelpi, E:
Med Univ Vienna, Dept Neurol, Div Neuropathol & Neurochem, Vienna, Austria
Rojas-García, R:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau IIB St Pau, Dept Neurol, Motor Neuron Dis Clin,Neuromuscular Dis Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona, Spain
Green Submitted, hybrid
|