title: Prevalence of spinocerebellar ataxia type 2 mutation among Italian Parkinsonian patients.
abstract: We evaluated the prevalence of the SCA2 mutation among 224 Italian patients affected by typical Parkinsonism, including 145 sporadic and 79 familial forms. Pink1, Parkin, and LRRK2 gene mutations had been excluded previously. Molecular testing for the CAG expansion at the SCA 2 locus was performed on leukocyte DNA. Cloning and sequencing of the expanded allele was performed in patients positive for the SCA2 expansion. A 38 CAG expansion was detected in 1 of 79 families studied. The proband, a male age 67, and his sister, age 69, were both affected by a benign form of L-dopa-responsive Parkinsonism not associated with cerebellar signs. The inheritance was autosomal dominant. The CAG expansion was stable through meiotic transmission: sequence analysis showed that the CAG stretch was interrupted by 3 CAA. Our study shows that CAG expansion at the SCA 2 locus may represent a genetic cause of familial L-dopa-responsive Parkinsonism among Italian patients. The stability of the pathological CAG expansion detected in this family was related to the presence of CAA interruptions. These findings, together with literature data, suggest that the molecular intrinsic structure of the expanded allele may modulate the phenotypic expression of the SCA2 mutation.
authors.affiliation: Department of Neuroscience, Catholic University, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Modoni
authors.forename: Maria Fiorella
authors.initials: MF
authors.lastname: Contarino
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bentivoglio
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Tabolacci
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Calcagni
authors.forename: Pietro A
authors.initials: PA
authors.lastname: Tonali
authors.forename: Giovanni
authors.initials: G
authors.lastname: Neri
authors.forename: Gabriella
authors.initials: G
authors.lastname: Silvestri
mesh_terms: D000067528:Ataxins; D005192:Family Health; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D011877:Radionuclide Imaging; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D014326:Tropanes / Q000378:metabolism
chemical_list: D000067528:Ataxins; D009419:Nerve Tissue Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane