Journal article
Whole exome sequencing in patients with white matter abnormalities
A Vanderver, C Simons, G Helman, J Crawford, NI Wolf, G Bernard, A Pizzino, JL Schmidt, A Takanohashi, D Miller, A Khouzam, V Rajan, E Ramos, S Chowdhury, T Hambuch, K Ru, GJ Baillie, SM Grimmond, L Caldovic, J Devaney Show all
Annals of Neurology | WILEY-BLACKWELL | Published : 2016
DOI: 10.1002/ana.24650
Abstract
Here we report whole exome sequencing (WES) on a cohort of 71 patients with persistently unresolved white matter abnormalities with a suspected diagnosis of leukodystrophy or genetic leukoencephalopathy. WES analyses were performed on trio, or greater, family groups. Diagnostic pathogenic variants were identified in 35% (25 of 71) of patients. Potentially pathogenic variants were identified in clinically relevant genes in a further 7% (5 of 71) of cases, giving a total yield of clinical diagnoses in 42% of individuals. These findings provide evidence that WES can substantially decrease the number of unresolved white matter cases.
Grants
Awarded by National Institutes of Health
Funding Acknowledgements
This work was supported by a Research Scholar Junior 1 Award from the Fonds de Recherche du Quebec en Sante (G.B.), an Australian Research Council Discovery Early Career Research Award (R.J.T.), a National Health and Medical Research Council, Australia grant (APP1068278), a University of Queensland Foundation Research Excellence Award, a ZonMw TOP Grant (91211005; N.I.W., M.S.v.d.K.), an NIH National Institute of Mental Health grant (K08MH086297; B.L.F.), an NIH National Institute of Neurological Disorders and Stroke grant (R01NS082094; B.L.F.), the Delman Fund for Pediatric Neurology and Education (G.H.), an award from the NIH National Center for Advancing Translational Sciences (UL1TR000075), and the Myelin Disorders Bioregistry Project (A.V., G.H., A.P., J.L.S., A.T., J.L.P.M.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Advancing Translational Sciences or the NIH. Computational support was provided by the NeCTAR Genomics Virtual Laboratory and QRIScloud programs.