Whole Exome Sequencing in Patients with White Matter Abnormalities

Adeline Vanderver; Cas Simons; Guy Helman; Joanna Crawford; Nicole I. Wolf; Genevieve 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; Raphael Schiffmann; Marjo S. van der Knaap; Ryan J. Taft

doi:10.1002/ana.24650

Whole Exome Sequencing in Patients with White Matter Abnormalities

Adeline Vanderver, Cas Simons, Guy Helman, Joanna Crawford, Nicole I. Wolf, Genevieve 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 DevaneyMiriam Bloom, Sarah H. Evans, Jennifer L. P. Murphy, Nathan McNeill, Brent L. Fogel, Raphael Schiffmann, Marjo S. van der Knaap, Ryan J. Taft

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	1031-1037
Journal	Annals of Neurology
Volume	79
Issue number	6
DOIs	https://doi.org/10.1002/ana.24650
Publication status	Published - Jun 2016

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10.1002/ana.24650

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Vanderver, A., Simons, C., Helman, G., Crawford, J., Wolf, N. I., Bernard, G., Pizzino, A., Schmidt, J. L., Takanohashi, A., Miller, D., Khouzam, A., Rajan, V., Ramos, E., Chowdhury, S., Hambuch, T., Ru, K., Baillie, G. J., Grimmond, S. M., Caldovic, L., ... Taft, R. J. (2016). Whole Exome Sequencing in Patients with White Matter Abnormalities. Annals of Neurology, 79(6), 1031-1037. https://doi.org/10.1002/ana.24650

@article{cf41297e608241f49d0ae9ab9557c72a,

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. ",

author = "Adeline Vanderver and Cas Simons and Guy Helman and Joanna Crawford and Wolf, {Nicole I.} and Genevieve Bernard and Amy Pizzino and Schmidt, {Johanna L.} and Asako Takanohashi and David Miller and Amirah Khouzam and Vani Rajan and Erica Ramos and Shimul Chowdhury and Tina Hambuch and Kelin Ru and Baillie, {Gregory J.} and Grimmond, {Sean M.} and Ljubica Caldovic and Joseph Devaney and Miriam Bloom and Evans, {Sarah H.} and Murphy, {Jennifer L. P.} and Nathan McNeill and Fogel, {Brent L.} and Raphael Schiffmann and {van der Knaap}, {Marjo S.} and Taft, {Ryan J.}",

year = "2016",

month = jun,

doi = "10.1002/ana.24650",

language = "English",

volume = "79",

pages = "1031--1037",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

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Vanderver, A, Simons, C, Helman, G, Crawford, J, Wolf, NI, Bernard, G, Pizzino, A, Schmidt, JL, Takanohashi, A, Miller, D, Khouzam, A, Rajan, V, Ramos, E, Chowdhury, S, Hambuch, T, Ru, K, Baillie, GJ, Grimmond, SM, Caldovic, L, Devaney, J, Bloom, M, Evans, SH, Murphy, JLP, McNeill, N, Fogel, BL, Schiffmann, R, van der Knaap, MS & Taft, RJ 2016, 'Whole Exome Sequencing in Patients with White Matter Abnormalities', Annals of Neurology, vol. 79, no. 6, pp. 1031-1037. https://doi.org/10.1002/ana.24650

TY - JOUR

T1 - Whole Exome Sequencing in Patients with White Matter Abnormalities

AU - Vanderver, Adeline

AU - Simons, Cas

AU - Helman, Guy

AU - Crawford, Joanna

AU - Wolf, Nicole I.

AU - Bernard, Genevieve

AU - Pizzino, Amy

AU - Schmidt, Johanna L.

AU - Takanohashi, Asako

AU - Miller, David

AU - Khouzam, Amirah

AU - Rajan, Vani

AU - Ramos, Erica

AU - Chowdhury, Shimul

AU - Hambuch, Tina

AU - Ru, Kelin

AU - Baillie, Gregory J.

AU - Grimmond, Sean M.

AU - Caldovic, Ljubica

AU - Devaney, Joseph

AU - Bloom, Miriam

AU - Evans, Sarah H.

AU - Murphy, Jennifer L. P.

AU - McNeill, Nathan

AU - Fogel, Brent L.

AU - Schiffmann, Raphael

AU - van der Knaap, Marjo S.

AU - Taft, Ryan J.

PY - 2016/6

Y1 - 2016/6

N2 - 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.

AB - 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.

U2 - 10.1002/ana.24650

DO - 10.1002/ana.24650

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