Intrafamilial variability of Parkinson phenotype in SCAs: Novel cases due to SCA2 and SCA3 expansions
| Autor: | Arlete Hilbig, Carlos Roberto de Mello Rieder, Laura Bannach Jardim, Maria Luiza Saraiva-Pereira, Vanessa Erichsen Emmel, Mariana Peixoto Socal |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Parkinson's disease Nerve Tissue Proteins Neurological examination Pedigree chart Disease Biology Antiparkinson Agents Levodopa medicine Humans Family Age of Onset Ataxin-3 Genes Dominant Spinocerebellar Degenerations Genetics DNA Repeat Expansion medicine.diagnostic_test Genetic heterogeneity Genetic Variation Nuclear Proteins Parkinson Disease Machado-Joseph Disease Middle Aged medicine.disease Phenotype Pedigree Repressor Proteins Ataxins Neurology Spinocerebellar ataxia Female Neurology (clinical) Geriatrics and Gerontology Age of onset |
| Zdroj: | Parkinsonism & Related Disorders. 15:374-378 |
| ISSN: | 1353-8020 |
| Popis: | Background: Parkinson’s disease (PD) has been related to mutations associated with spinocerebellar ataxias (SCA); the frequency of the diagnosis of these mutations is low in general late-onset PD cases. Our aim was to investigate a selected high-risk group of PD patients. Methods: PD patients with autosomal dominant inheritance or atypical neurological manifestations were enrolled, underwent a full neurological examination and had the CAG tracts of their SCA1, 2, 3, 6 and 7 genes analyzed. Results: Of the 23 studied families, two SCA3 and one SCA2 cases were identified. All had autosomal dominant inheritance. In the SCA2 pedigree, four affected sibs had a homogeneous PD phenotype. CAG repeats varied between 35 and 44 with CAA interruptions. Intrafamilial phenotypic heterogeneity was identified in the SCA3 pedigrees; parkinsonian and ataxic phenotypes coexisted in both kindreds. CAGn varied between 69 and 71 repeats. Age of onset was lower in the SCA3 patients than in the remaining 24 cases (38 versus 46.7 � 12 years of age, p ¼ 0.003). Conclusions: SCA2 and SCA3 mutations were detected in 13% of the present sample: the strategy of selecting a high-risk group increased the rate of making these diagnoses. The SCA2 cases confirmed an association between PD and interrupted expansions, as well as PD intrafamilial phenotypic homogeneity. Clinical heterogeneity of SCA3 pedigrees suggests that disease-modifying agents outside the MJD1 gene may play a role in determining PD symptoms in this disorder. |
| Databáze: | OpenAIRE |
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