Protein and gene expression analysis of Phf6, the gene mutated in the Börjeson-Forssman-Lehmann Syndrome of intellectual disability and obesity

Anne K. Voss, Robin Gamble, Caitlin Collin, Cheryl Shoubridge, Mark Corbett, Jozef Gécz, Tim Thomas

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33 Citations (Scopus)


The Plant homeodomain finger gene 6 (PHF6) was identified as the gene mutated in patients suffering from the Börjeson-Forssman-Lehmann Syndrome (BFLS), an X-linked mental retardation disorder. BFLS mental disability is evident from an early age, suggesting a developmental brain defect. The PHF6 protein contains four nuclear localisation signals and two imperfect plant homeodomain (PHD) fingers similar to the third, imperfect PHD fingers in members of the trithorax family of transcriptional regulators. The PHF6 gene is highly conserved in vertebrate species. Despite the devastating effects of mutation of the PHF6 gene, nothing is known about the cellular function of PHF6. In order to lay the base for functional studies, we identify here the cell types that express the murine Phf6 gene and protein during prenatal and postnatal development. The Phf6 gene and protein are expressed widely. However, expression levels vary from strong to barely detectable. Strongest Phf6 gene expression and nuclear localisation of Phf6 protein were observed in the developing central nervous system, the anterior pituitary gland, the primordia of facial structures and the limb buds. Expression levels of both mRNA and protein decline over the course of development. In the adult brain moderate Phf6 expression is maintained in projection neurons, such as mitral cells in the olfactory bulb, cerebrocortical pyramidal cells and cerebellar Purkinje cells. Phf6 gene expression and nuclear localisation of Phf6 protein correlate with clinical symptoms in BFLS patients, namely mental disability, pan-anterior pituitary hormonal deficiency and facial as well digit abnormalities.

Original languageEnglish
Pages (from-to)858-871
Number of pages14
JournalGene Expression Patterns
Issue number8
Publication statusPublished or Issued - Oct 2007


  • BFLS
  • Brain development
  • Börjeson-Forssman-Lehmann Syndrome
  • Cerebral cortex
  • Digit abnormalities
  • Facial abnormalities
  • Genital hypoplasia
  • Growth retardation
  • Gynecomastia
  • Hypophysis
  • Hypotonia
  • Mental retardation
  • Nuclear protein
  • Nucleus
  • Obesity
  • PHD
  • Phf6
  • Pituitary gland
  • Plant homeodomain finger gene 6
  • Spermatogenesis
  • X-linked syndrome

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology

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