English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality

Belet, S., Fieremans, N., Yuan, X., Van Esch, H., Verbeeck, J., Ye, Z., et al. (2014). Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality. Human Mutation, 35(3), 350-355. doi:10.1002/humu.22498.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-BC95-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-BC96-A
Genre: Journal Article

Files

show Files
hide Files
:
Belet.pdf (Publisher version), 703KB
Name:
Belet.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2014 John Wiley & Sons, Inc.
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Belet, S., Author
Fieremans, N., Author
Yuan, X., Author
Van Esch, H., Author
Verbeeck, J., Author
Ye, Z., Author
Cheng, L., Author
Brodsky, B. R., Author
Hu, H.1, Author              
Kalscheuer, V. M.2, Author              
Brodsky, R. A., Author
Froyen, G., Author
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
2Chromosome Rearrangements and Disease (Vera Kalscheuer), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479642              

Content

show
hide
Free keywords: Chromosomes, Human, X/genetics Exome Exons Female *Frameshift Mutation *Genes, X-Linked Germ-Line Mutation Humans Intellectual Disability/*genetics/mortality Male Membrane Proteins/*genetics Pedigree Phenotype Sequence Analysis, DNA
 Abstract: The phosphatidylinositol glycan class A (PIGA) protein is a member of the glycosylphosphatidylinositol anchor pathway. Germline mutations in PIGA located at Xp22.2 are thought to be lethal in males. However, a nonsense mutation in the last coding exon was recently described in two brothers with multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2) who survived through birth likely because of the hypomorphic nature of the truncated protein, but died in their first weeks of life. Here, we report on a frameshift mutation early in the PIGA cDNA (c.76dupT; p.Y26Lfs*3) that cosegregates with the disease in a large family diagnosed with a severe syndromic form of X-linked intellectual disability. Unexpectedly, CD59 surface expression suggested the production of a shorter PIGA protein with residual functionality. We provide evidence that the second methionine at position 37 may be used for the translation of a 36 amino acids shorter PIGA. Complementation assays confirmed that this shorter PIGA cDNA was able to partially rescue the surface expression of CD59 in a PIGA-null cell line. Taken together, our data strongly suggest that the early frameshift mutation in PIGA produces a truncated hypomorph, which is sufficient to rescue the lethality in males but not the MCAHS2-like phenotype.

Details

show
hide
Language(s): eng - English
 Dates: 2014-01-132014-03
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/humu.22498
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: 35 (3) Sequence Number: - Start / End Page: 350 - 355 Identifier: ISSN: 1059-7794
CoNE: https://pure.mpg.de/cone/journals/resource/954925597586