Hyperphosphatasia mental retardation (HPMR) syndrome is an autosomal recessive form of mental retardation with distinct facial features and elevated serum alkaline phosphatase. We performed whole-exome sequencing in three siblings of a nonconsanguineous union with HPMR and performed computational inference of regions identical by descent in all siblings to establish PIGV, encoding a member of the GPI-anchor biosynthesis pathway, as the gene mutated in HPMR. We identified homozygous or compound heterozygous mutations in PIGV in three additional families.
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Ng, S.B. et al. Nat. Genet. 42, 30–35 (2010).
Ng, S.B. et al. Nature 461, 272–276 (2009).
Roach, J.C. et al. Science 328, 636–639 (2010).
Mabry, C.C. et al. J. Pediatr. 77, 74–85 (1970).
Kruse, K., Hanefeld, F., Kohlschutter, A., Rosskamp, R. & Gross-Selbeck, G. J. Pediatr. 112, 436–439 (1988).
Horn, D., Schottmann, G. & Meinecke, P. Eur. J. Med. Genet. 53, 85–88 (2010).
McQuillan, R. et al. Am. J. Hum. Genet. 83, 359–372 (2008).
Rabe, P. et al. Am. J. Med. Genet. 41, 350–354 (1991).
Marcelis, C.L., Rieu, P., Beemer, F. & Brunner, H.G. Clin. Dysmorphol. 16, 73–76 (2007).
Thompson, M.D. et al. Am. J. Med. Genet. 152A, 1661–1669 (2010).
Kang, J.Y. et al. J. Biol. Chem. 280, 9489–9497 (2005).
Kinoshita, T., Fujita, M. & Maeda, Y. J. Biochem. 144, 287–294 (2008).
Nozaki, M. et al. Lab. Invest. 79, 293–299 (1999).
Takeda, J. et al. Cell 73, 703–711 (1993).
Almeida, A.M. et al. Nat. Med. 12, 846–851 (2006).
This work was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 665) to S.M., by a grant from Bundesministerium für Bildung und Forschung (BMBF, project number 0313911) and an Australian National Health and Medical Research Council international research training fellowship to T.R., and by a grant of the Canadian Institutes of Health Research and Epilepsy Canada to M.D.T. We thank B. Fischer, U. Kornak, M. Ralser, E. van Beusekom, U. Marchfelder and D. Lefeber for their assistance in this project.
The authors declare no competing financial interests.
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Krawitz, P., Schweiger, M., Rödelsperger, C. et al. Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome. Nat Genet 42, 827–829 (2010). https://doi.org/10.1038/ng.653
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