title: Whole exome sequencing in patients with white matter abnormalities.
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.
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington, DC.|Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC.|School of Medicine and Health Sciences, George Washington University, Washington, DC.
authors.forename: Adeline
authors.initials: A
authors.lastname: Vanderver
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Cas
authors.initials: C
authors.lastname: Simons
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington, DC.|Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC.
authors.forename: Guy
authors.identifier: http://orcid.org/0000-0002-4784-7423
authors.initials: G
authors.lastname: Helman
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Joanna
authors.initials: J
authors.lastname: Crawford
authors.affiliation: Department of Child Neurology, VU University Medical Center and Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
authors.affiliation: Departments of Pediatrics, Neurology, and Neurosurgery, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bernard
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington, DC.
authors.forename: Amy
authors.initials: A
authors.lastname: Pizzino
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington, DC.|Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC.
authors.forename: Johanna L
authors.initials: JL
authors.lastname: Schmidt
authors.affiliation: Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC.
authors.forename: Asako
authors.initials: A
authors.lastname: Takanohashi
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia.|University of Melbourne Centre for Cancer Research, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Miller
authors.affiliation: Illumina Inc, San Diego, CA.
authors.forename: Amirah
authors.initials: A
authors.lastname: Khouzam
authors.affiliation: Illumina Inc, San Diego, CA.
authors.forename: Vani
authors.initials: V
authors.lastname: Rajan
authors.affiliation: Illumina Inc, San Diego, CA.
authors.forename: Erica
authors.initials: E
authors.lastname: Ramos
authors.affiliation: Illumina Inc, San Diego, CA.
authors.forename: Shimul
authors.initials: S
authors.lastname: Chowdhury
authors.affiliation: Illumina Inc, San Diego, CA.
authors.forename: Tina
authors.initials: T
authors.lastname: Hambuch
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Kelin
authors.initials: K
authors.lastname: Ru
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Baillie
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia.|University of Melbourne Centre for Cancer Research, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.affiliation: Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC.
authors.forename: Ljubica
authors.initials: L
authors.lastname: Caldovic
authors.affiliation: Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC.
authors.forename: Joseph
authors.initials: J
authors.lastname: Devaney
authors.affiliation: Department of Pediatrics, Children's National Medical Center, Washington, DC.
authors.forename: Miriam
authors.initials: M
authors.lastname: Bloom
authors.affiliation: Department of Physical Medicine and Rehabilitation, Children's National Medical Center, Washington, DC.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Evans
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington, DC.
authors.forename: Jennifer L P
authors.initials: JLP
authors.lastname: Murphy
authors.affiliation: Institute for Metabolic Disease, Baylor Research Institute, Dallas, TX.
authors.forename: Nathan
authors.initials: N
authors.lastname: McNeill
authors.affiliation: Department of Neurology, Program in Neurogenetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
authors.forename: Brent L
authors.initials: BL
authors.lastname: Fogel
authors.affiliation: Institute for Metabolic Disease, Baylor Research Institute, Dallas, TX.
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.affiliation: Department of Child Neurology, VU University Medical Center and Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.|Department of Functional Genomics, VU University, Amsterdam, the Netherlands.
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
authors.affiliation: School of Medicine and Health Sciences, George Washington University, Washington, DC.|Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia.|Illumina Inc, San Diego, CA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Taft
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D066127:White Matter / Q000473:pathology*; D055815:Young Adult