Expanded Phenotypic Definition Identifies Hundreds of Potential Causative Genes for Leukodystrophies and Leukoencephalopathies

[摘要] Background: The genes responsible for genetic white matter disorders (GWMD; leukodystrophies and leukoencephalopathies)are incompletely known. Our goal was to revise the list of genes considered to cause GWMD. We considered a GWMD toconsist of any genetic disease causing T2 signal white matter changes in magnetic resonance images. Methods and Results:Using a systematic review of PubMed, Google, published literature reviews, and commercial gene panels, we identified 399 uniquegenes meeting the GWMD definition. Of this, 87 (22%) genes were hypomyelinating. Only 3 genes had contrast enhancement onmagnetic resonance imaging (MRI): ABCD1, GFAP, and UNC13D. Conclusions: A significantly greater number of genes thanpreviously recognized, 399, are associated with white matter signal changes on T2 MRI. This expansion of GWMD genes can beuseful in analysis and interpretation of next-generation sequencing results for GWMD diagnosis, and for understanding sharedpathophysiological mechanisms of GWMDs.

[学科分类] 电子与电气工程

[关键词] leukodystrophy;genes;leukoencephalopathy;classification;diagnosis