English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO

Skopkova, M., Hennig, F., Shin, B. S., Turner, C. E., Stanikova, D., Brennerova, K., et al. (2017). EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO. Human Mutation, 38(4), 409-425. doi:10.1002/humu.23170.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0000-78AD-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-5975-7
Genre: Journal Article

Files

show Files
hide Files
:
Skopkova.pdf (Publisher version), 2MB
Name:
Skopkova.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2017 John Wiley & Sons, Inc.
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Skopkova, M., Author
Hennig, F.1, Author              
Shin, B. S., Author
Turner, C. E., Author
Stanikova, D., Author
Brennerova, K., Author
Stanik, J., Author
Fischer, U.2, Author              
Henden, L., Author
Müller, U., Author
Steinberger, D., Author
Leshinsky-Silver, E., Author
Bottani, A., Author
Kurdiova, T., Author
Ukropec, J., Author
Nyitrayova, O., Author
Kolnikova, M., Author
Klimes, I., Author
Borck, G., Author
Bahlo, M., Author
Haas, S. A.3, Author              Kim, J. R., AuthorLotspeich-Cole, L. E., AuthorGasperikova, D., AuthorDever, T. E., AuthorKalscheuer, V. M.1, Author               more..
Affiliations:
1Chromosome Rearrangements and Disease (Vera Kalscheuer), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385702              
2Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
3Gene Structure and Array Design (Stefan Haas), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479640              

Content

show
hide
Free keywords: Eif2s3 MEHMO syndrome Xlid integrated stress response translation initiation unfolded-protein response
 Abstract: Impairment of translation initiation and its regulation within the integrated stress response (ISR) and related unfolded-protein response has been identified as a cause of several multisystemic syndromes. Here, we link MEHMO syndrome, whose genetic etiology was unknown, to this group of disorders. MEHMO is a rare X-linked syndrome characterized by profound intellectual disability, epilepsy, hypogonadism and hypogenitalism, microcephaly, and obesity. We have identified a C-terminal frameshift mutation (Ile465Serfs) in the EIF2S3 gene in three families with MEHMO syndrome and a novel maternally inherited missense EIF2S3 variant (c.324T>A; p.Ser108Arg) in another male patient with less severe clinical symptoms. The EIF2S3 gene encodes the gamma subunit of eukaryotic translation initiation factor 2 (eIF2), crucial for initiation of protein synthesis and regulation of the ISR. Studies in patient fibroblasts confirm increased ISR activation due to the Ile465Serfs mutation and functional assays in yeast demonstrate that the Ile465Serfs mutation impairs eIF2gamma function to a greater extent than tested missense mutations, consistent with the more severe clinical phenotype of the Ile465Serfs male mutation carriers. Thus, we propose that more severe EIF2S3 mutations cause the full MEHMO phenotype, while less deleterious mutations cause a milder form of the syndrome with only a subset of the symptoms.

Details

show
hide
Language(s): eng - English
 Dates: 2017-01-232017-04
 Publication Status: Published in print
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1002/humu.23170
ISSN: 1098-1004 (Electronic)1059-7794 (Print)
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Human Mutation
  Other : Hum Mut
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York, N.Y. : Wiley-Liss
Pages: - Volume / Issue: 38 (4) Sequence Number: - Start / End Page: 409 - 425 Identifier: ISSN: 1059-7794
CoNE: /journals/resource/954925597586