Author’s Response to “Classifying Hypomyelination: A Critical (white) Matter” From Perrier et al.: regarding Expanded Phenotypic Definition Identifies Hundreds of Potential Causative Genes for Leukodystrophies and Leukoencephalopathies

摘要

We thank Perrier, Matovic, and Bernard for their very insightful letter regarding topics identified in our article.1 The objective of our work wastoidentify and include all genes that have been reported to cause T2 white matter abnormalities. We wanted to develop a more complete list of genes associated with leukodystrophies and leukoencephalopathies, which we termed “genetic white matter disorders (GWMD).” Previous publications have taken more restrictive definitions of leukodystrophies and GWMD,2-4 despite the absence of unambiguous, consistent, defining genetic or biochemical features Perrier et al. identify several limitations in our article, and we agree with their insights. In particular, they point out that it is essential to differentiate delayed or slow myelination from true hypomyelination; and that for some disorders the MRI images are lacking or with insufficient quality or timepoints. Another great point they raise is that some of the disorders are treatable, such as phenylketonuria, and require prompt identification and therapy.