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

Parastoo Momeni, Gernot Glöckner, Olaf Schmidt, Diane Von Holtum, Beate Albrecht, Gabriele Gillessen-Kaesbach, Raoul Hennekam, Peter Meinecke, Bernhard Zabel, André Rosenthal, Bernhard Horsthemke, Hermann Josef Lüdecke*

*Corresponding author for this work
231 Citations (Scopus)


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; refs 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. TRPS1 has 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.

Original languageEnglish
JournalNature Genetics
Issue number1
Pages (from-to)71-74
Number of pages4
Publication statusPublished - 2000

Research Areas and Centers

  • Research Area: Medical Genetics


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