Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome

Nat Genet. 2002 Dec;32(4):661-5. doi: 10.1038/ng1040. Epub 2002 Nov 4.


Börjeson-Forssman-Lehmann syndrome (BFLS; OMIM 301900) is characterized by moderate to severe mental retardation, epilepsy, hypogonadism, hypometabolism, obesity with marked gynecomastia, swelling of subcutaneous tissue of the face, narrow palpebral fissure and large but not deformed ears. Previously, the gene associated with BFLS was localized to 17 Mb in Xq26-q27 (refs 2-4). We have reduced this interval to roughly 9 Mb containing more than 62 genes. Among these, a novel, widely expressed zinc-finger (plant homeodomain (PHD)-like finger) gene (PHF6) had eight different missense and truncation mutations in seven familial and two sporadic cases of BFLS. Transient transfection studies with PHF6 tagged with green fluorescent protein (GFP) showed diffuse nuclear staining with prominent nucleolar accumulation. Such localization, and the presence of two PHD-like zinc fingers, is suggestive of a role for PHF6 in transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Cell Nucleolus / metabolism
  • Cell Nucleus / metabolism
  • Embryo, Mammalian / metabolism
  • Female
  • Genetic Predisposition to Disease*
  • Green Fluorescent Proteins
  • HeLa Cells
  • Heterozygote
  • Humans
  • Intellectual Disability / genetics*
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Microsatellite Repeats
  • Molecular Sequence Data
  • Mutation*
  • Mutation, Missense
  • Pedigree
  • Physical Chromosome Mapping
  • Sequence Alignment
  • Syndrome
  • Transfection
  • X Chromosome
  • Zinc Fingers


  • Luminescent Proteins
  • Green Fluorescent Proteins

Associated data

  • GENBANK/AB058726
  • GENBANK/AC004383
  • GENBANK/AK016480
  • GENBANK/AL591668
  • GENBANK/AW153989
  • GENBANK/AW421659
  • GENBANK/AW767237
  • GENBANK/AY157622
  • GENBANK/BE507109
  • RefSeq/NP_115711