DESCRIPTION:

A Kleefstra Syndrome patient’s known pathogenic EHMT1 genetic variant, EHMT1_c.3430C > T; p.Gln1144* (referred to as EHMT1_SNV) was introduced into iPSCs by CRISPR single base editing, followed by neuronal cell differentiation. IPSCs were induced for neural differentiation to form neural progenitor cells (NPCs). Kleefstra syndrome is caused by EHMT1 haploinsufficiency that results in partial or complete loss of EHMT1 expression. Expression was compared between NPC_SNV and iPSC_SNV respectively. Expression values were calculated by the method detailed in 'HBA-DEALS: accurate and simultaneous identification of differential expression and splicing using hierarchical Bayesian analysis' (Genome Biol. 2020, PMID: 32660516), and log base 2 of the fold change are presented with a FDR of <0.05. Up regulated genes were annotated as Ensembl gene ids. SRA Study id SRP325023. Experimental Factor Ontology EFO:EFO_0010976; KOLF2-C1.

LABEL:

Up regulated genes from NPC_SNV compared to iPSC_SNV

SCORE TYPE:

Effect

DATE ADDED:

2023-06-21

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Vanessa S Fear, Catherine A Forbes, Denise Anderson, Sebastian Rauschert, Genevieve Syn, Nicole Shaw, Sarra Jamieson, Michelle Ward, Gareth Baynam, Timo Lassmann

TITLE:

CRISPR single base editing, neuronal disease modelling and functional genomics for genetic variant analysis: pipeline validation using Kleefstra syndrome EHMT1 haploinsufficiency.

JOURNAL:

Stem cell research & therapy Feb 2022, Vol 13, pp. 69

ABSTRACT:

Over 400 million people worldwide are living with a rare disease. Next Generation Sequencing (NGS) identifies potential disease causative genetic variants. However, many are identified as variants of uncertain significance (VUS) and require functional laboratory validation to determine pathogenicity, and this creates major diagnostic delays. PUBMED: 35139903
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