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Whole exome sequencing in patients with white matter abnormalities
Author(s) -
Vanderver Adeline,
Simons Cas,
Helman Guy,
Crawford Joanna,
Wolf Nicole I.,
Bernard Geneviève,
Pizzino Amy,
Schmidt Johanna L.,
Takanohashi Asako,
Miller David,
Khouzam Amirah,
Rajan Vani,
Ramos Erica,
Chowdhury Shimul,
Hambuch Tina,
Ru Kelin,
Baillie Gregory J.,
Grimmond Sean M.,
Caldovic Ljubica,
Devaney Joseph,
Bloom Miriam,
Evans Sarah H.,
Murphy Jennifer L. P.,
McNeill Nathan,
Fogel Brent L.,
Schiffmann Raphael,
van der Knaap Marjo S.,
Taft Ryan J.
Publication year - 2016
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24650
Subject(s) - exome sequencing , leukodystrophy , leukoencephalopathy , white matter , exome , cohort , medicine , medical genetics , pathology , biology , genetics , mutation , gene , magnetic resonance imaging , disease , radiology
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