English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation

Khayat, W., Hackett, A., Shaw, M., Ilie, A., Dudding-Byth, T., Kalscheuer, V. M., et al. (2019). A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation. Human Molecular Genetics, 28(4), 598-614. doi:10.1093/hmg/ddy371.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0002-5F72-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-5558-B
Genre: Journal Article

Files

show Files
hide Files
:
Khayat.pdf (Publisher version), 10MB
Name:
Khayat.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© The Author(s) 2018
License:
-

Locators

show

Creators

show
hide
 Creators:
Khayat, Wujood, Author
Hackett , Anna, Author
Shaw, Marie, Author
Ilie , Alina, Author
Dudding-Byth , Tracy, Author
Kalscheuer, Vera M.1, Author              
Christie , Louise , Author
Corbett , Mark A., Author
Juusola , Jane, Author
Friend, Kathryn L. , Author
Kirmse , Brian M., Author
Gecz , Jozef, Author
Field, Michael, Author
Orlowski, John, Author
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              

Content

show
hide
Free keywords: -
 Abstract: We report two unrelated families with multigenerational nonsyndromic intellectual disability segregating with a recurrent de novo missense variant (c.1543C>T:p.Leu515Phe) in the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7). SLC9A7 is located on human X chromosome at Xp11.3 and has not yet been associated with a human phenotype. The gene is widely transcribed, but especially abundant in brain, skeletal muscle and various secretory tissues. Within cells, SLC9A7 resides in the Golgi apparatus, with prominent enrichment in the trans-Golgi network (TGN) and post-Golgi vesicles. In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG. This correlated with alkalinization of the TGN/post-Golgi compartments, suggestive of a gain-of-function. Membrane trafficking of glycosylation-deficient Leu515Phe and co-transfected VSVG to the cell surface, however, was relatively unaffected. Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation. These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked intellectual

Details

show
hide
Language(s): eng - English
 Dates: 2018-10-122018-10-172019-02-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1093/hmg/ddy371
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Human Molecular Genetics
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Oxford, England : IRL Press
Pages: 17 Volume / Issue: 28 (4) Sequence Number: - Start / End Page: 598 - 614 Identifier: ISSN: 0964-6906
CoNE: https://pure.mpg.de/cone/journals/resource/954925581153