Whole exome sequencing in patients with white matter abnormalities.
Adeline VanderverCas SimonsGuy HelmanJoanna CrawfordNicole I WolfGeneviève BernardAmy PizzinoJohanna L SchmidtAsako TakanohashiDavid MillerAmirah KhouzamVani RajanErica RamosShimul ChowdhuryTina HambuchKelin RuGregory J BaillieSean M GrimmondLjubica CaldovicJoseph DevaneyMiriam BloomSarah H EvansJennifer L P MurphyNathan McNeillBrent L Fogelnull nullRaphael SchiffmannMarjo S van der KnaapRyan J TaftPublished in: Annals of neurology (2016)
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.