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

Authors

  • Sarah Teixeira Camargos MD,

    1. Movement Disorders Group, Neurology Service, Department of Internal Medicine, Federal University of Minas Gerais, Minas Gerais, Brazil
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  • Leonardo Oliveira Dornas MD,

    1. Movement Disorders Group, Neurology Service, Department of Internal Medicine, Federal University of Minas Gerais, Minas Gerais, Brazil
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  • Parastoo Momeni PhD,

    1. Department of Neurology, Texas Tech University Health Sciences Center, Texas, USA
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  • Andrew Lees MD, PhD,

    1. Reta Lila Weston Institute of Neurological Studies, University College London, London, United Kingdom
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  • John Hardy PhD,

    1. Reta Lila Weston Institute of Neurological Studies, University College London, London, United Kingdom
    2. Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, United Kingdom
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  • Andrew Singleton PhD,

    1. Laboratory of Neurogenetics, National Institutes on Aging, National Institutes of Health, Maryland, USA
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  • Francisco Cardoso MD, PhD

    Corresponding author
    1. Movement Disorders Group, Neurology Service, Department of Internal Medicine, Federal University of Minas Gerais, Minas Gerais, Brazil
    • Av Pasteur 89/1107, Belo Horizonte, MG, Brazil
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  • Potential conflict of interest: None reported.

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. © 2009 Movement Disorder Society

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