Article (Scientific journals)
Broadening the phenotypic spectrum and physiological insights related to EIF2S3 variants.
Moortgat, Stephanie; Manfroid, Isabelle; Pendeville-Samain, Hélène et al.
2021In Human Mutation, 42 (7), p. 827-834
Peer Reviewed verified by ORBi
 

Files


Full Text
humu.24215.pdf
Publisher postprint (2.73 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
CRISPR/Cas9; EIF2S3; MEHMO syndrome; apoptosis; zebrafish
Abstract :
[en] Mental deficiency, epilepsy, hypogonadism, microcephaly, and obesity syndrome is a severe X-linked syndrome caused by pathogenic variants in EIF2S3. The gene encodes the γ subunit of the eukaryotic translation initiation factor-2, eIF2, essential for protein translation. A recurrent frameshift variant is described in severely affected patients while missense variants usually cause a moderate phenotype. We identified a novel missense variant (c.433A>G, p.(Met145Val)) in EIF2S3 in a mildly affected patient. Studies on zebrafish confirm the pathogenicity of this novel variant and three previously published missense variants. CRISPR/Cas9 knockout of eif2s3 in zebrafish embryos recapitulate the human microcephaly and show increased neuronal cell death. Abnormal high glucose levels were identified in mutant embryos, caused by beta cell and pancreatic progenitor deficiency, not related to apoptosis. Additional studies in patient-derived fibroblasts did not reveal apoptosis. Our results provide new insights into disease physiopathology, suggesting tissue-dependent mechanisms.
Disciplines :
Pediatrics
Anatomy (cytology, histology, embryology...) & physiology
Genetics & genetic processes
Author, co-author :
Moortgat, Stephanie
Manfroid, Isabelle ;  Université de Liège - ULiège > GIGA Stem Cells - Zebrafish Dev. & Disease Model
Pendeville-Samain, Hélène ;  Université de Liège - ULiège > GIGA Platform Zebrafish facility & transgenics
Freeman, Stephen 
Bourdouxhe, Jordane 
Benoit, Valérie
Merhi, Ahmad
Philippe, Christophe
Faivre, Laurence
Maystadt, Isabelle
Language :
English
Title :
Broadening the phenotypic spectrum and physiological insights related to EIF2S3 variants.
Publication date :
2021
Journal title :
Human Mutation
ISSN :
1059-7794
eISSN :
1098-1004
Publisher :
John Wiley & Sons, Hoboken, United States - New Jersey
Volume :
42
Issue :
7
Pages :
827-834
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
© 2021 Wiley Periodicals LLC.
Available on ORBi :
since 23 September 2021

Statistics


Number of views
52 (2 by ULiège)
Number of downloads
3 (3 by ULiège)

Scopus citations®
 
4
Scopus citations®
without self-citations
4
OpenCitations
 
4

Bibliography


Similar publications



Contact ORBi