Genome sequencing in persistently unsolved white matter disorders. Issue 1 (7th January 2020)

• Record Type: Journal Article
• Authors: Helman, Guy; Lajoie, Bryan R.; Crawford, Joanna; Takanohashi, Asako; Walkiewicz, Marzena; Dolzhenko, Egor; Gross, Andrew M.; Gainullin, Vladimir G.; Bent, Stephen J.; Jenkinson, Emma M.; Ferdinandusse, Sacha; Waterham, Hans R.; Dorboz, Imen; Bertini, Enrico; Miyake, Noriko; Wolf, Nicole I.; Abbink, Truus E. M.; Kirwin, Susan M.; Tan, Christina M.; Hobson, Grace M.; Guo, Long; Ikegawa, Shiro; Pizzino, Amy; Schmidt, Johanna L.; Bernard, Genevieve; Schiffmann, Raphael; van der Knaap, Marjo S.; Simons, Cas; Taft, Ryan J.; Vanderver, Adeline
• Is Part Of: Annals of clinical and translational neurology. Volume 7:Issue 1(2020)
• Page Start: 144
• Page End: 152
• Publication Date: 2020-01-07
• Subjects: Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1002/acn3.50957
• Languages: English
• ISSNs: 2328-9503

Abstract

Abstract: Genetic white matter disorders have heterogeneous etiologies and overlapping clinical presentations. We performed a study of the diagnostic efficacy of genome sequencing in 41 unsolved cases with prior exome sequencing, resolving an additional 14 from an historical cohort ( n = 191). Reanalysis in the context of novel disease‐associated genes and improved variant curation and annotation resolved 64% of cases. The remaining diagnoses were directly attributable to genome sequencing, including cases with small and large copy number variants (CNVs) and variants in deep intronic and technically difficult regions. Genome sequencing, in combination with other methodologies, achieved a diagnostic yield of 85% in this retrospective cohort.