Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome

Nat Genet. 2010 Oct;42(10):827-9. doi: 10.1038/ng.653. Epub 2010 Aug 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • CHO Cells
  • Child, Preschool
  • Cricetinae
  • Cricetulus
  • Databases, Genetic
  • Exons / genetics*
  • Family Health
  • Female
  • Genetic Predisposition to Disease*
  • Glycosylphosphatidylinositols / metabolism
  • Humans
  • Hyperphosphatemia / genetics*
  • Infant
  • Intellectual Disability / genetics*
  • Male
  • Mannosyltransferases / genetics*
  • Mutation / genetics*
  • Open Reading Frames / genetics
  • Syndrome
  • Transfection


  • Glycosylphosphatidylinositols
  • Mannosyltransferases
  • PIGV protein, human