title: Familial Parkinsonism and early onset Parkinson's disease in a Brazilian movement disorders clinic: phenotypic characterization and frequency of SNCA, PRKN, PINK1, and LRRK2 mutations.
abstract: The aim of the study was to evaluate the frequency and to perform phenotypic and genotypic characterization of familial Parkinsonism and early onset Parkinson's disease (EOPD) in a Brazilian movement disorder unit. We performed a standardized clinical assessment of patients followed by sequencing of PRKN, PINK1 in EOPD cases and SNCA, LRRK2 in familial Parkinsonism individuals. During the period of study (January through December, 2006), we examined 575 consecutive patients of whom 226 (39.3%) met the diagnosis of Parkinsonism and idiopathic Parkinson's disease (IPD) was diagnosed in 202 of the latter. Of the IPD cases, 45 (22.3%) had EOPD. The age at onset in the EOPD cases (n = 45) was 34.8 +/- 5.4 years (mean +/- standard deviation). The age at onset in the familial late-onset PD patients (n = 8) was 52.3 +/- 12.2 years. In the early onset cases, we identified five known mutations in PRKN, two single heterozygous and three compound heterozygous (P153R, T240M, 255Adel, W54R, V3I); in addition, we identified one novel mutation in PINK1 (homozygous deletion of exon 7). In the familial cases (late onset), 1 patient had a novel LRRK2 variant, Q923H, but no SNCA mutations were identified. We have demonstrated that EOPD accounts for a high frequency of IPD cases in our tertiary referral center. PRKN was the most commonly mutated gene, but we also identified a novel mutation in PINK1 and a novel variant in LRRK2.
authors.affiliation: Movement Disorders Group, Neurology Service, Department of Internal Medicine, Federal University of Minas Gerais, Minas Gerais, Brazil.
authors.forename: Sarah Teixeira
authors.initials: ST
authors.lastname: Camargos
authors.forename: Leonardo Oliveira
authors.initials: LO
authors.lastname: Dornas
authors.forename: Parastoo
authors.initials: P
authors.lastname: Momeni
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: Francisco
authors.initials: F
authors.lastname: Cardoso
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000596:Amino Acids / Q000235:genetics; D001938:Brazil / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics*; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000596:Amino Acids; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C497604:SNCA protein, human; C111567:parkin protein; C495280:LRRK2 protein, human