de.mpg.escidoc.pubman.appbase.FacesBean
English
 
Help Guide Disclaimer Contact us Login
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Mutations in PIGO, a member of the GPI-anchor-synthesis pathway, cause hyperphosphatasia with mental retardation

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons50196

Hecht,  J.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;
Berlin Brandenburg Center for Regenerative Therapies, Charité Universitätsmedizin;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50380

Kielbasa,  S. M.
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50437

Mundlos,  S.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;
Berlin Brandenburg Center for Regenerative Therapies, Charité Universitätsmedizin;
Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50496

Robinson,  P. N.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;
Berlin Brandenburg Center for Regenerative Therapies, Charité Universitätsmedizin;
Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin;

Locator
There are no locators available
Fulltext (public)

Krawitz.pdf
(Publisher version), 636KB

Supplementary Material (public)
There is no public supplementary material available
Citation

Krawitz, P. M., Murakami, Y., Hecht, J., Kruger, U., Holder, S. E., Mortier, G. R., et al. (2012). Mutations in PIGO, a member of the GPI-anchor-synthesis pathway, cause hyperphosphatasia with mental retardation. American Journal of Human Genetics, 91(1), 146-151. doi:10.1016/j.ajhg.2012.05.004.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-F270-E
Abstract
Hyperphosphatasia with mental retardation syndrome (HPMRS), an autosomal-recessive form of intellectual disability characterized by facial dysmorphism, seizures, brachytelephalangy, and persistent elevated serum alkaline phosphatase (hyperphosphatasia), was recently shown to be caused by mutations in PIGV, a member of the glycosylphosphatidylinositol (GPI)-anchor-synthesis pathway. However, not all individuals with HPMRS harbor mutations in this gene. By exome sequencing, we detected compound-heterozygous mutations in PIGO, a gene coding for a membrane protein of the same molecular pathway, in two siblings with HPMRS, and we then found by Sanger sequencing further mutations in another affected individual; these mutations cosegregated in the investigated families. The mutant transcripts are aberrantly spliced, decrease the membrane stability of the protein, or impair enzyme function such that GPI-anchor synthesis is affected and the level of GPI-anchored substrates localized at the cell surface is reduced. Our data identify PIGO as the second gene associated with HPMRS and suggest that a deficiency in GPI-anchor synthesis is the underlying molecular pathomechanism of HPMRS.