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.

中文翻译：

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持续未解决的白质疾病的基因组测序。

遗传性白质疾病具有异质性病因和重叠的临床表现。我们对 41 例未解决的病例进行了基因组测序的诊断功效研究，这些病例之前进行了外显子组测序，解决了历史队列中的另外 14 例 ( n  = 191)。在新的疾病相关基因和改进的变异管理和注释的背景下重新分析解决了 64% 的病例。其余诊断直接归因于基因组测序，包括具有小拷贝数变异和大拷贝数变异 (CNV) 以及深层内含子和技术困难区域中的变异的病例。基因组测序与其他方法相结合，在这个回顾性队列中实现了 85% 的诊断率。