Mutations in PIGO, a Member of the GPI-Anchor-Synthesis Pathway, Cause Hyperphosphatasia with Mental Retardation
書誌事項
- 公開日
- 2012-07
- 資源種別
- journal article
- 権利情報
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- https://www.elsevier.com/tdm/userlicense/1.0/
- https://www.elsevier.com/legal/tdmrep-license
- http://www.elsevier.com/open-access/userlicense/1.0/
- DOI
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- 10.1016/j.ajhg.2012.05.004
- 公開者
- Elsevier BV
この論文をさがす
説明
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.
収録刊行物
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- The American Journal of Human Genetics
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The American Journal of Human Genetics 91 (1), 146-151, 2012-07
Elsevier BV
