Open AccessGenome sequencing in persistently unsolved white matter disorders
Author(s) -
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,
Knaap Marjo S.,
Simons Cas,
Taft Ryan J.,
Vanderver Adeline
Publication year - 2020
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.50957
Subject(s) - exome sequencing , dna sequencing , medicine , context (archaeology) , genome , exome , whole genome sequencing , genomics , genetics , computational biology , copy number variation , deep sequencing , gene , biology , mutation , paleontology
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.