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

• Published in: Brain sciences Vol. 11; no. 7; p. 904
• Main Authors: Brand, Boudewien A, Blesson, Alyssa E, Smith-Hicks, Constance L.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 09.07.2021; MDPI
• Subjects: Ataxia; Congenital diseases; Convulsions & seizures; Epilepsy; Females; FMR1; FMR1 protein; fragile X syndrome; FXTAS; Gene expression; Genotype & phenotype; Intellectual disabilities; Language disorders; Learning disabilities; Males; MECP2; MeCP2 protein; Methyl-CpG binding protein; Microcephaly; Neurodevelopmental disorders; Phenotypes; Rett syndrome; Review; Spasticity; X chromosomes; X-chromosome inactivation
• ISSN: 2076-3425; 2076-3425
• DOI: 10.3390/brainsci11070904

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.