title: Genetic polymorphism of MJD1 alleles and molecular analysis of SCA3 patients from Rio de Janeiro, Brazil.
abstract: Spinocerebellar ataxia type 3 is the most common form of autosomal dominant cerebellar ataxia. It is a severe progressive neurological disorder caused by an expansion of an exonic CAG repeat of the MJD1 gene. The repeated sequence is polymorphic among both normal individuals and patients. In general, expanded alleles are paternally inherited and the disorder exhibits anticipation. We performed a PCR-based study to determine polymorphisms of the number of CAG repeats of the MJD1 gene in an anonymous sample of normal Brazilian individuals. We also analyzed DNA samples from 9 patients with ataxia. We identified 29 different allele sizes ranging from 12 to 40 CAG repeats, with heterozygosity of 79%. The distribution of allele sizes showed two major peaks of 16 (7%) and 26 (10.1%) CAG repeats. When grouping normal alleles by size, we observed that the distribution varies between males and females, and a significant deviation from the Hardy-Weinberg equilibrium was observed with an excess of normal large alleles among males. We also detected expanded alleles with 68-73 CAG repeats in 3 out of 9 ataxic patients.
authors.affiliation: Serviço de Genética Humana, Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors.forename: Raquel S
authors.initials: RS
authors.lastname: Gestinari
authors.forename: Stenio F P
authors.initials: SF
authors.lastname: Duarte
authors.forename: Márcia M G
authors.initials: MM
authors.lastname: Pimentel
authors.forename: Marcelo A Costa
authors.initials: MA
authors.lastname: Lima
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000067699:Ataxin-3; D001938:Brazil; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D017827:Machado-Joseph Disease / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D011110:Polymorphism, Genetic; D012097:Repressor Proteins; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3