Journal
JOURNAL OF THE NEUROLOGICAL SCIENCES
Volume 383, Issue -, Pages 18-25Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jns.2017.10.010
Keywords
Cerebrotendinous xanthomatosis; Diagnosis; Hereditary spastic paraplegia HSP; Next-generation sequencing; SPG
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [460941/2014-3]
- Fundo de Incentivo a Pesquisa e Eventos-Hospital de Clinicas de Porto Alegre (FIPE-HCPA) [14-0695]
- CNPq
- Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
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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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