A de novo balanced translocation t(7;12)(p21.2;p12.3) in a patient with Saethre-Chotzen-like phenotype downregulates TWIST and an osteoclastic protein-tyrosine phosphatase, PTP-oc

Eur J Med Genet. Sep-Oct 2011;54(5):e478-83. doi: 10.1016/j.ejmg.2011.05.007. Epub 2011 Jun 25.


Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome with variable expression. Here we report on a female infant with a de novo balanced translocation 46, XX, t(7;12)(p21.2;p12.3) and presenting at birth brachycephaly, antimongolic palpebral fissures, ocular hypertelorism, broad nose with low nasal bridge and low-set ears. This phenotype is suggestive of a subtle form of SCS, given the absence of limbs anomalies. Cloning of both breakpoints revealed that the translocation does not interrupt the TWIST1 coding region, on 7p21, known to be causative for SCS, but downregulates TWIST1 expression due to a position effect. On chromosome 12, the breakpoint translocates a shorter transcript of PTPRO gene, the osteoclastic protein-tyrosine phosphatase, PTP-oc, near to regulatory region of 7p leading to down-regulation of PTP-oc in the proband's fibroblasts. This is a confirmatory case report providing further evidence for TWIST1 haploinsufficiency in SCS, although a possible role of PTP-oc as genetic factor underlying or at least influencing the development of craniosynostosis could not be a priori excluded.

Publication types

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

MeSH terms

  • Acrocephalosyndactylia / diagnosis
  • Acrocephalosyndactylia / genetics*
  • Brain / pathology
  • Child, Preschool
  • Chromosome Breakpoints
  • Chromosome Mapping
  • Chromosomes, Human, Pair 12 / genetics
  • Chromosomes, Human, Pair 7 / genetics
  • CpG Islands / genetics
  • DNA Methylation / genetics
  • Down-Regulation / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Infant
  • Karyotyping
  • Mutation / genetics
  • Phenotype*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / genetics*
  • Receptors, Fibroblast Growth Factor / genetics
  • Translocation, Genetic / genetics*
  • Twist-Related Protein 1 / genetics*


  • Receptors, Fibroblast Growth Factor
  • Twist-Related Protein 1
  • PTPRO protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3