title: Mutational screening of 320 Brazilian patients with autosomal dominant spinocerebellar ataxia.
abstract: Autosomal dominant spinocerebellar ataxias (SCAs) are a clinical and genetically heterogeneous group of debilitating neurodegenerative diseases that are related to at least 36 different genetic loci; they are clinically characterized by progressive cerebellar ataxia and are frequently accompanied by other neurological and non-neurological manifestations. The relative frequency of SCA varies greatly among different regions, presumably because of a founder effect or local ethnicities. Between July 1998 and May 2012, we investigated 320 Brazilian patients with an SCA phenotype who belonged to 150 unrelated families with an autosomal dominant inheritance pattern and 23 sporadic patients from 13 Brazilian states. A total of 265 patients (82.8%) belonging to 131 unrelated families (87.3%) were found to have a definite mutation, and SCA3 accounted for most of the familial cases (70.7%), followed by SCA7 (6%), SCA1 (5.3%), SCA2 (2.7%), SCA6 (1.3%), SCA8 (0.7%) and SCA10 (0.7%). In the Ribeirão Preto mesoregion, which is located in the northeast part of São Paulo State, the prevalence of SCA3 was approximately 5 per 100,000 inhabitants, which is the highest prevalence found in Brazil. No mutation was found in the SCA12, SCA17 and DRPLA genes, and all the sporadic cases remained without a molecular diagnosis. This study further characterizes the spectrum of SCA mutations found in Brazilian patients, which suggests the existence of regional differences and demonstrates the expansion of the SCA8 locus in Brazilian families.
authors.affiliation: Ribeirão Preto School of Medicine, University of São Paulo, Department of Neurosciences and Behavior Sciences, Av. Bandeirantes 3900, Campus da USP - Monte Alegre, Ribeirão Preto, SP Zip Code 14049-900, Brazil.
authors.forename: Vívian Pedigone
authors.initials: VP
authors.lastname: Cintra
authors.affiliation: Ribeirão Preto School of Medicine, University of São Paulo, Department of Neurosciences and Behavior Sciences, Av. Bandeirantes 3900, Campus da USP - Monte Alegre, Ribeirão Preto, SP Zip Code 14049-900, Brazil.
authors.forename: Charles Marques
authors.initials: CM
authors.lastname: Lourenço
authors.affiliation: Ribeirão Preto School of Medicine, University of São Paulo, Department of Neurosciences and Behavior Sciences, Av. Bandeirantes 3900, Campus da USP - Monte Alegre, Ribeirão Preto, SP Zip Code 14049-900, Brazil.
authors.forename: Sandra Elisabete
authors.initials: SE
authors.lastname: Marques
authors.affiliation: Ribeirão Preto School of Medicine, University of São Paulo, Department of Neurosciences and Behavior Sciences, Av. Bandeirantes 3900, Campus da USP - Monte Alegre, Ribeirão Preto, SP Zip Code 14049-900, Brazil.
authors.forename: Luana Michelli
authors.initials: LM
authors.lastname: de Oliveira
authors.affiliation: Ribeirão Preto School of Medicine, University of São Paulo, Department of Neurosciences and Behavior Sciences, Av. Bandeirantes 3900, Campus da USP - Monte Alegre, Ribeirão Preto, SP Zip Code 14049-900, Brazil.
authors.forename: Vitor
authors.initials: V
authors.lastname: Tumas
authors.affiliation: Ribeirão Preto School of Medicine, University of São Paulo, Department of Neurosciences and Behavior Sciences, Av. Bandeirantes 3900, Campus da USP - Monte Alegre, Ribeirão Preto, SP Zip Code 14049-900, Brazil. Electronic address: wmarquesjunior@gmail.com.
authors.forename: Wilson
authors.initials: W
authors.lastname: Marques
mesh_terms: D000328:Adult; D001938:Brazil / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D020754:Spinocerebellar Ataxias / Q000145:classification* / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
keywords: Machado-Joseph disease; Mutational frequency; Mutational prevalence; Repeat expansion; Spinocerebellar ataxia