Frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese patients with amyotrophic lateral sclerosis.
Marta Gromicho, Susana Pinto, Eugeniu Gisca, Ana Catarina Pronto-Laborinho, Peter M Andersen, Mamede de Carvalho
Author Information
Marta Gromicho: Instituto de Medicina Molecular and Institute of Physiology, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisbon, Portugal. Electronic address: martalgms@gmail.com.
Susana Pinto: Instituto de Medicina Molecular and Institute of Physiology, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisbon, Portugal; Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
Eugeniu Gisca: Instituto de Medicina Molecular and Institute of Physiology, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisbon, Portugal.
Ana Catarina Pronto-Laborinho: Instituto de Medicina Molecular and Institute of Physiology, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisbon, Portugal.
Peter M Andersen: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
Mamede de Carvalho: Instituto de Medicina Molecular and Institute of Physiology, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisbon, Portugal; Department of Neurosciences and Mental Health, Hospital de Santa Maria-CHLN, Lisbon, Portugal.
Mutation frequency of the 2 main amyotrophic lateral sclerosis (ALS)-related genes, C9orf72 and SOD1, varies considerably across the world. We analyzed those genes in a large population of Portuguese ALS patients (n = 371) and recorded demographic and clinical features. Familial ALS (FALS) was disclosed in 11.6% of patients. Mutations in either SOD1 or C9orf72 were found in 9.2% of patients and accounted for 40% of FALS and 5.2% of sporadic ALS. SOD1 mutations were rare (0.83%), but a novel and probably disease-causing mutation was identified: p.Ala152Pro (c.457G>C). The C9orf72 hexanucleotide repeat expansion was the commonest abnormality, accounting for 4.6% of sporadic ALS and 37.5% of FALS; in these patients, Frontotemporal Dementia was prevalent. This first report on the frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese ALS patients reiterate that the genetic architecture of ALS varies among different geographic regions. The mutations incidence in ALS patients (∼10%) and associated phenotypes suggest that genetic tests should be offered to more patients, and other genes should be investigated in our population.
