Transcriptome data of temporal and cingulate cortex in the Rett syndrome brain

Kimberly A Aldinger,Oleg V Evgrafov,Jennifer S Herstein,James A Knowles,James W Macdonald,Hanna K Mcnamara,Andrew E Timms,Theo K Bammler,Pat Levitt

doi:10.1038/s41597-020-0527-2

Abstract

Rett syndrome is an X-linked neurodevelopmental disorder caused by mutation in the methyl-CpG-binding protein 2 gene (MECP2) in the majority of cases. We describe an RNA sequencing dataset of postmortem brain tissue samples from four females clinically diagnosed with Rett syndrome and four age-matched female donors. The dataset contains 16 transcriptomes, including two brain regions, temporal and cingulate cortex, for each individual. We compared our dataset with published transcriptomic analyses of postmortem brain tissue from Rett syndrome and found consistent gene expression alterations among regions of the cerebral cortex. Our data provide a valuable resource to explore the biology of the human brain in Rett syndrome.

Highlights

Background & SummaryRett syndrome (RTT) is an X-linked neurodevelopmental disorder mostly caused by heterozygous de novo mutation in the methyl-CpG-binding protein 2 gene (MECP2) and predominantly affecting females[1]
These clinical disorders illustrate the critical requirement for proper MECP2 expression in human brain development, though how MeCP2 dysfunction leads to the RTT phenotype is unclear
One study used both microarrays and RNA sequencing (RNA-seq) to examine frontal and temporal cortex from individuals with RTT compared to controls and identified over 200 differentially expressed genes after normalizing data for neuron versus glia composition of samples[13]

Summary

Background & Summary

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder mostly caused by heterozygous de novo mutation in the methyl-CpG-binding protein 2 gene (MECP2) and predominantly affecting females[1]. MeCP2 may be required for fine-tuning the gene expression for a network of protein-coding genes through both direct and indirect mechanisms Consistent with this hypothesis, small magnitude changes in gene expression have been detected in brain tissue from either human postmortem RTT samples or mouse Mecp2-mutants[9,10,11,12]. Most transcriptional studies of postmortem RTT brain have used microarray platforms with small numbers and a lack of age-matched control samples, which impact the sensitivity for detecting transcriptional changes One study used both microarrays and RNA sequencing (RNA-seq) to examine frontal and temporal cortex from individuals with RTT compared to controls and identified over 200 differentially expressed genes after normalizing data for neuron versus glia composition of samples[13]. The composite analysis will be useful to facilitate interpretation and further understanding of MECP2-mediated changes in human brain

Methods

Findings

Code availability