Mutations in a new gene, encoding a zinc-finger protein, cause tricho-rhino-phalangeal syndrome type I

Nat Genet. 2000 Jan;24(1):71-4. doi: 10.1038/71717.


Tricho-rhino-phalangeal syndrome type I (TRPS I, MIM 190350) is a malformation syndrome characterized by craniofacial and skeletal abnormalities and is inherited in an autosomal dominant manner. TRPS I patients have sparse scalp hair, a bulbous tip of the nose, a long flat philtrum, a thin upper vermilion border and protruding ears. Skeletal abnormalities include cone-shaped epiphyses at the phalanges, hip malformations and short stature. We assigned TRPS1 to human chromosome 8q24. It maps proximal of EXT1, which is affected in a subgroup of patients with multiple cartilaginous exostoses and deleted in all patients with TRPS type II (TRPS II, or Langer-Giedion syndrome, MIM 150230; ref.2-5). We have positionally cloned a gene that spans the chromosomal breakpoint of two patients with TRPS I and is deleted in five patients with TRPS I and an interstitial deletion. Northern-blot analyses revealed transcripts of 7 and 10.5 kb. TRPS1has seven exons and an ORF of 3,843 bp. The predicted protein sequence has two potential nuclear localization signals and an unusual combination of different zinc-finger motifs, including IKAROS-like and GATA-binding sequences. We identified six different nonsense mutations in ten unrelated patients. Our findings suggest that haploinsufficiency for this putative transcription factor causes TRPS I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Chromosome Mapping
  • Chromosomes, Human, Pair 8
  • DNA, Complementary
  • Female
  • Humans
  • Langer-Giedion Syndrome / genetics*
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Open Reading Frames
  • Pedigree
  • Zinc Fingers / genetics*


  • DNA, Complementary

Associated data

  • GENBANK/AA470941
  • GENBANK/AA662457
  • GENBANK/AF178030
  • GENBANK/AF183810
  • GENBANK/H50546
  • GENBANK/H53479
  • GENBANK/H53854
  • GENBANK/R54193
  • GENBANK/R83254