Clinical and molecular characterization of hereditary spastic paraplegias: A next-generation sequencing panel approach.
J Neurol Sci
; 383: 18-25, 2017 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-29246610
BACKGROUND: Molecular diagnosis of hereditary spastic paraplegias (HSP) is a difficult task due to great clinical and genetic heterogeneity. We aimed to characterize clinical and molecular findings of HSP families from Rio Grande do Sul, Brazil; and to evaluate the diagnostic yield of a next-generation sequencing (NGS) panel with twelve HSP-related genes. METHODS: A consecutive series of HSP index cases with familial recurrence of spasticity, consanguinity or thin corpus callosum (TCC) were included in this cross-sectional study. RESULTS: Among the 29 index cases, 51.7% (15/29) received at least a likely molecular diagnosis, and 48.3% (14/29) a defined diagnosis. NGS panel diagnostic yield was 60% for autosomal dominant HSP (6/10, all SPG4), 47.4% for autosomal recessive HSP (9/19: 5 SPG11, 2 SPG7, 1 SPG5 and 1 cerebrotendinous xanthomatosis), and 50% for patients with TCC (3/6, all SPG11). Remarkably, 2/6 SPG11 patients presented keratoconus, and tendon xanthomas were absent in the patient with cerebrotendinous xanthomatosis. CONCLUSION: A likely molecular diagnosis was obtained for more than half of families with the NGS panel, indicating that this approach could be employed as a first-line investigation for HSP. SPG4 is the most frequent form of autosomal dominant and SPG11 of autosomal recessive HSP in Southern Brazil.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paraplegia Espástica Hereditária
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Testes Genéticos
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Sequenciamento de Nucleotídeos em Larga Escala
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
J Neurol Sci
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Holanda