Heterozygous nonsense mutation SATB2 associated with cleft palate, osteoporosis, and cognitive defects

Hum Mutat. 2007 Jul;28(7):732-8. doi: 10.1002/humu.20515.


Studies of human chromosomal aberrations and knockout (KO) mice have suggested SATB2 as a candidate gene for a human malformation syndrome of craniofacial patterning and brain development. Of 59 unrelated patients with craniofacial dysmorphism, with or without mental retardation, one 36-year-old man had a nonsynonymous mutation in SATB2. The affected individual exhibited craniofacial dysmorphisms including cleft palate, generalized osteoporosis, profound mental retardation, epilepsy and a jovial personality. He carries a de novo germline nonsense mutation (c.715C>T, p.R239X) in the exon 6 of SATB2. Expression studies showed that the mutant RNA was stable, expected to produce a truncated protein predicted to retain its dimerization domain and exert a dominant negative effect. This new syndrome is the first determined to result from mutation of a gene within the family that encodes nuclear matrix-attachment region (MAR) proteins.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Cleft Palate / genetics*
  • Codon, Nonsense*
  • Cognition Disorders / genetics*
  • DNA Primers
  • Exons
  • Heterozygote*
  • Humans
  • Male
  • Matrix Attachment Region Binding Proteins / genetics*
  • Osteoporosis / genetics*
  • Polymerase Chain Reaction
  • Transcription Factors / genetics*


  • Codon, Nonsense
  • DNA Primers
  • Matrix Attachment Region Binding Proteins
  • SATB2 protein, human
  • Transcription Factors