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

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.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F270-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F271-C
Genre: Journal Article

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© 2012 The American Society of Human Genetics. Published by Elsevier Inc.
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 Creators:
Krawitz, P. M., Author
Murakami, Y., Author
Hecht, J.1, 2, Author              
Kruger, U., Author
Holder, S. E., Author
Mortier, G. R., Author
Delle Chiaie, B., Author
De Baere, E., Author
Thompson, M. D., Author
Roscioli, T., Author
Kielbasa, S. M.3, Author              
Kinoshita, T., Author
Mundlos, S.1, 2, 4, Author              
Robinson, P. N.1, 2, 4, Author              
Horn, D., Author              
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1433557              
2Berlin Brandenburg Center for Regenerative Therapies, Charité Universitätsmedizin, Berlin, Germany, ou_persistent22              
3Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1433547              
4Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin, Berlin, Germany, ou_persistent22              

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Free keywords: Adolescent Alkaline Phosphatase/ blood Child Child, Preschool Female Humans Infant Intellectual Disability/ genetics Membrane Proteins/ genetics Models, Molecular Mutation Pedigree Syndrome
 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.

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Language(s): eng - English
 Dates: 2012-06-072012-07-13
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.ajhg.2012.05.004
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Title: American Journal of Human Genetics
Source Genre: Journal
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Publ. Info: American Society of Human Genetics
Pages: - Volume / Issue: 91 (1) Sequence Number: - Start / End Page: 146 - 151 Identifier: ISSN: 0002-9297
CoNE: https://pure.mpg.de/cone/journals/resource/954925377893