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Whole exome sequencing in patients with white matter abnormalities |
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| Authors: | Adeline Vanderver MD Cas Simons PhD Guy Helman BS Joanna Crawford MS Nicole I. Wolf MD PhD Geneviève Bernard MD Amy Pizzino MS GCG Johanna L. Schmidt MPH MGC Asako Takanohashi DVM PhD David Miller BAppSc Amirah Khouzam MS MA CGC Vani Rajan MS Erica Ramos MS LCGC Shimul Chowdhury PhD Tina Hambuch PhD Kelin Ru MS Gregory J. Baillie PhD Sean M. Grimmond PhD Ljubica Caldovic PhD Joseph Devaney PhD Miriam Bloom MD Sarah H. Evans MD Jennifer L. P. Murphy MS CPNP‐AC Nathan McNeill MS Brent L. Fogel MD PhD the Leukodystrophy Study Group Raphael Schiffmann MD Marjo S. van der Knaap MD PhD Ryan J. Taft PhD |
| Affiliation: | 1. Department of Neurology, Children's National Medical Center, Washington, DC;2. Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC;3. School of Medicine and Health Sciences, George Washington University, Washington, DC;4. Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia;5. Department of Child Neurology, VU University Medical Center and Neuroscience Campus Amsterdam, Amsterdam, the Netherlands;6. Departments of Pediatrics, Neurology, and Neurosurgery, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada;7. University of Melbourne Centre for Cancer Research, University of Melbourne, Parkville, Victoria, Australia;8. Illumina Inc, San Diego, CA;9. Department of Pediatrics, Children's National Medical Center, Washington, DC;10. Department of Physical Medicine and Rehabilitation, Children's National Medical Center, Washington, DC;11. Institute for Metabolic Disease, Baylor Research Institute, Dallas, TX;12. Department of Neurology, Program in Neurogenetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA;13. Department of Functional Genomics, VU University, Amsterdam, the Netherlands |
| 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. Ann Neurol 2016;79:1031–1037 |
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