Whole exome sequencing in patients with white matter abnormalities
Adeline Vanderver, Cas Simons, Guy Helman, Joanna Crawford, Nicole I Wolf, Geneviève Bernard, Amy Pizzino, Johanna L Schmidt, Asako Takanohashi, David Miller, Amirah Khouzam, Vani Rajan, Erica Ramos, Shimul Chowdhury, Tina Hambuch, Kelin Ru, Gregory J Baillie, Sean M Grimmond, Ljubica Caldovic, Joseph Devaney, Miriam Bloom, Sarah H Evans, Jennifer L P Murphy, Nathan McNeill, Brent L Fogel, Leukodystrophy Study Group, Raphael Schiffmann, Marjo S van der Knaap, Ryan J Taft, Andrea L Gropman, Tena Rosser, Phillip L Pearl, Eva Fung, Sumit Parikh, Bruce H Cohen, James D Reggin, Cengiz Yalcinkaya, Yuval Shafrir, MarcDiFazio, Emily Freilich, Charles M Lourenco, Carolina Tesi-Rocha, Jay Desai, Hernan Amartino, K Nicole Weaver, Valynne Long, Michael J Gambello, Melissa L Cirillo, Ilana Kahn, Deepak Gill, Maria Gieron, Emily de Los Reyes, Bennett Lavenstein, Brendan C Lanpher, Gerhard Kurleman, Adeline Vanderver, Cas Simons, Guy Helman, Joanna Crawford, Nicole I Wolf, Geneviève Bernard, Amy Pizzino, Johanna L Schmidt, Asako Takanohashi, David Miller, Amirah Khouzam, Vani Rajan, Erica Ramos, Shimul Chowdhury, Tina Hambuch, Kelin Ru, Gregory J Baillie, Sean M Grimmond, Ljubica Caldovic, Joseph Devaney, Miriam Bloom, Sarah H Evans, Jennifer L P Murphy, Nathan McNeill, Brent L Fogel, Leukodystrophy Study Group, Raphael Schiffmann, Marjo S van der Knaap, Ryan J Taft, Andrea L Gropman, Tena Rosser, Phillip L Pearl, Eva Fung, Sumit Parikh, Bruce H Cohen, James D Reggin, Cengiz Yalcinkaya, Yuval Shafrir, MarcDiFazio, Emily Freilich, Charles M Lourenco, Carolina Tesi-Rocha, Jay Desai, Hernan Amartino, K Nicole Weaver, Valynne Long, Michael J Gambello, Melissa L Cirillo, Ilana Kahn, Deepak Gill, Maria Gieron, Emily de Los Reyes, Bennett Lavenstein, Brendan C Lanpher, Gerhard Kurleman
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.
Conflict of interest statement
Potential Conflicts of Interest
AV receives funding from Illumina, Inc., Gilead Sciences Inc., Eli Lilly & Co. and Shire Plc. AK, VR, ER, SC, TH, and RJT are employees of Illumina, Inc. The rest of the authors report no conflict of interest.
© 2016 American Neurological Association.
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Source: PubMed