Normalized Clinical Severity Scores Reveal a Correlation between X Chromosome Inactivation and Disease Severity in Rett Syndrome.

ABSTRACT: Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing the MECP2 allele resides on the paternal X chromosome while a healthy copy is maintained on the maternal X chromosome with inactivation (XCI), resulting in mosaic expression of one allele in each cell. Preferential inactivation of the paternal X chromosome is theorized to result in reduced disease severity; however, establishing such a correlation is complicated by known MECP2 genotype effects and an age-dependent increase in severity. To mitigate these confounding factors, we developed an age- and genotype-normalized measure of RTT sev

SUBMITTER: Merritt JK 

PROVIDER: S-EPMC11120815 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature