The Impact of X-Chromosome Inactivation on Phenotypic Expression of X-Linked Neurodevelopmental Disorders

Boudewien A Brand; Alyssa E Blesson; Constance L Smith-Hicks

doi:10.3390/brainsci11070904

The Impact of X-Chromosome Inactivation on Phenotypic Expression of X-Linked Neurodevelopmental Disorders

Brain Sci. 2021 Jul 9;11(7):904. doi: 10.3390/brainsci11070904.

Authors

Boudewien A Brand¹, Alyssa E Blesson¹, Constance L Smith-Hicks^{2

3}

Affiliations

¹ Center for Autism and Related Disorders, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
² Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
³ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Abstract

Nearly 20% of genes located on the X chromosome are associated with neurodevelopmental disorders (NDD) due to their expression and role in brain functioning. Given their location, several of these genes are either subject to or can escape X-chromosome inactivation (XCI). The degree to which genes are subject to XCI can influence the NDD phenotype between males and females. We provide a general review of X-linked NDD genes in the context of XCI and detailed discussion of the sex-based differences related to MECP2 and FMR1, two common X-linked causes of NDD that are subject to XCI. Understanding the effects of XCI on phenotypic expression of NDD genes may guide the development of stratification biomarkers in X-linked disorders.

Keywords: FMR1; FXTAS; MECP2; POI; Rett syndrome; X-chromosome inactivation; fragile X syndrome; neurodevelopmental disorders.

Publication types

Review