Clinical and genetic characterization of leukoencephalopathies in adults
Carregando...
Citações na Scopus
77
Tipo de produção
article
Data de publicação
2017
Editora
OXFORD UNIV PRESS
Indexadores
Título da Revista
ISSN da Revista
Título do Volume
Autores
LYNCH, David S.
ZHANG, Wei Jia
BUGIARDINI, Enrico
MACEDO-SOUZA, Lucia Ines
LAKSHMANAN, Rahul
KINSELLA, Justin A.
MERWICK, Aine
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
BRAIN, v.140, p.1204-1211, 2017
Resumo
Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all. In this study, we used focused and whole exome sequencing to evaluate a cohort of undiagnosed adult patients referred to a specialist leukoencephalopathy service. In total, 100 patients were evaluated using focused exome sequencing of 6100 genes. We detected pathogenic or likely pathogenic variants in 26 cases. The most frequently mutated genes were NOTCH3, EIF2B5, AARS2 and CSF1R. We then carried out whole exome sequencing on the remaining negative cases including four family trios, but could not identify any further potentially disease-causing mutations, confirming the equivalence of focused and whole exome sequencing in the diagnosis of genetic leukoencephalopathies. Here we provide an overview of the clinical and genetic features of these disorders in adults.
Palavras-chave
leukodystrophy, neurodegeneration, white matter lesion, imaging
Referências
- Ahmed RM, 2014, J NEUROL NEUROSUR PS, V85, P770, DOI 10.1136/jnnp-2013-305888
- Dallabona C, 2014, NEUROLOGY, V82, P2063, DOI 10.1212/WNL.0000000000000497
- Hurst S, 2006, GENET MED, V8, P371, DOI 10.1097/01.gim.0000223551.95862.c3
- Lynch DS, 2016, JAMA NEUROL, V114, P494
- Parikh S, 2015, MOL GENET METAB, V114, P501, DOI 10.1016/j.ymgme.2014.12.434
- Rademakers R, 2012, NAT GENET, V44, P200, DOI 10.1038/ng.1027
- Richards J, 2015, AM J MED GENET A, V167, P2541, DOI 10.1002/ajmg.a.37215
- Richards S, 2015, GENET MED, V17, P405, DOI 10.1038/gim.2015.30
- Scheper GC, 2007, NAT GENET, V39, P534, DOI 10.1038/ng2013
- van Rappard DF, 2016, NEUROLOGY, V87, P103, DOI 10.1212/WNL.0000000000002811
- Vanderver A, 2016, ANN NEUROL, V79, P1031, DOI 10.1002/ana.24650
- Vanderver A, 2015, MOL GENET METAB, V114, P494, DOI 10.1016/j.ymgme.2015.01.006
- Wang K, 2010, NUCLEIC ACIDS RES, V38, pe164, DOI 10.1093/NAR/GKQ603