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Zebrafish modeling mimics developmental phenotype of patients with RAPGEF1 mutation

Authors: 
Li N, Zhou P, Yang M, Fang X, Krämer N, Mughal TA, Abbasi AA, Yang Y, Kaindl AM, Hu H
Citation: 
Clin Genet. 2021 Apr 9. doi: 10.1111/cge.13965. Online ahead of print
Abstract: 
RAPGEF1 is a guanine nucleotide exchange factor responsible for transmitting extracellular signals to the Ras family of GTPase located at the inside of membrane. Here, we report for the first time a homozygous mutation of RAPGEF1 in a consanguineous family with two siblings affected by neuropsychiatric disorder. To confirm the correlation of the mutation and the phenotype, we utilized in silico analysis and established a zebrafish model. Survival rate was reduced in the rapgef1a-knockdown model, and the zebrafish showed global morphological abnormalities, particularly of brain and blood vessels. Co-application of human RAPGEF1 wildtype mRNA effectively rescued the abnormal phenotype, while that of RAPGEF1 mRNA carrying the human mutation did not. This work is the first report of a human Mendelian disease associated with RAPGEF1 and the first report of a zebrafish model built for this gene. The phenotype of zebrafish model provides further evidence that defective RAPGEF1 may lead to global developmental delay in human patients.
Epub: 
Yes
Organism or Cell Type: 
zebrafish
Delivery Method: 
microinjection