Interconnected Gene Networks Underpin the Clinical Overlap of HNRNPH1-Related and Rubinstein-Taybi Intellectual Disability Syndromes.

Luciano Calzari,Lidia Larizza,Silvia Russo,Valentina Alari

doi:10.3389/fnins.2021.745684

Abstract

Interconnected Gene Networks Underpin the Clinical Overlap of HNRNPH1-Related and Rubinstein-Taybi Intellectual Disability Syndromes.

Highlights

The transcriptome of induced pluripotent stem cell-neurons generated from patients with neurodevelopmental disorders (NDDs) is a quantitative phenotype that provides the biological context for unveiling the molecular pathways disrupted in the “diseased” cells
downregulated genes (DRGs) for RNA-processing proteins, involved in ribosome complex biogenesis include those for the polypeptides D1, F, D2, G, and D3 making up the structural core of small nuclear ribonucleoproteins of the eukaryotic premRNA splicing machinery (Figure 1A)
Data from transcriptome analysis of RSTS neurons definitely connects CBP/p300 deficit to dysfunction of a coherent network of RNA-binding proteins (RBPs) involved in RNA processing and ribosome complex biogenesis (Calzari et al, 2020; Larizza et al, 2022)

Summary

Introduction

The transcriptome of induced pluripotent stem cell (iPSC)-neurons (iNeurons) generated from patients with neurodevelopmental disorders (NDDs) is a quantitative phenotype that provides the biological context for unveiling the molecular pathways disrupted in the “diseased” cells. RNASeq of iNeurons from individuals with Rubinstein–Taybi syndrome (RSTS, MIM# 180849, and #613684), an intellectual disability (ID) disorder caused by monoallelic pathogenic variants in the genes encoding CBP/p300 lysine acetyltransferases (Hennekam, 2006), revealed that RSTS-univocal downregulated genes (DRGs) encoding a coherent network of RNA-binding proteins (RBPs) are implicated in RNA processing and ribosome complex biogenesis (Calzari et al, 2020).

Results

Conclusion