Hereditary spastic paraplegia 3A associated with axonal neuropathy.
Arch Neurol
; 64(5): 706-13, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17502470
ABSTRACT
OBJECTIVE:
To study the frequency and distribution of mutations in SPG3A in a large cohort of patients with hereditary spastic paraplegia.DESIGN:
We screened a large cohort of 182 families and isolated cases with pure or complex hereditary spastic paraplegia phenotypes, which were negative for mutations in SPG4.RESULTS:
In 12 probands (6.6%), we identified 12 different SPG3A mutations (11 missense and 1 insertion/frameshift) of which 7 were novel and 3 were de novo. We found incomplete penetrance in 1 family (G482V). In most cases, SPG3A mutations were associated with an early age at onset (mean, 3 y); however, in 1 family (R495W mutation), symptoms started later (mean, 14 y) with clear intrafamilial variability (8-28 y). Six patients with an SPG3A mutation (F151S, Q191R, M408T, G469A, R495W) originating from 5 unrelated families presented with a complex form of hereditary spastic paraplegia associated with a neuropathy (17%). Our electrophysiological and pathological findings confirmed an axonal sensory-motor neuropathy. There was no correlation between the genotype and the presence of a neuropathy.CONCLUSIONS:
We conclude that mutations in SPG3A represent an important cause of patients in the overall hereditary spastic paraplegia population. SPG3A is more often associated with a neuropathy than previously assumed. Therefore, patients with a bipyramidal syndrome and a neuropathy should be screened for mutations in SPG3A.
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Bases de dados:
MEDLINE
Assunto principal:
Polineuropatias
/
Paraplegia Espástica Hereditária
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Predisposição Genética para Doença
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Proteínas de Transporte Vesicular
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Proteínas de Membrana
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Mutação
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Arch Neurol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Bulgária