CYLD mutation causes multiple familial trichoepithelioma in three Chinese families

Hum Mutat. 2004 Apr;23(4):400. doi: 10.1002/humu.9231.

Abstract

Multiple familial trichoepithelioma (MFT) and familial cylindromatosis are two clinically distinct cancer syndromes. MFT patients developed mostly trichoepithelioma in the face while cylindromatosis patients developed cylindromas predominantly (approximately 90%) on the head and neck. However, multiple familial trichoepithelioma is occasionally associated with familial cylindromatosis while cylindromatosis patients can also develop trichoepithelioma. This has led to the speculation that the 2 types of dermatoses may be caused by dysfunction of a common pathway. Previously, a candidate MTF locus has been mapped to 9p21 while disease gene for familial cylindromatosis, the CYLD gene located on 16q21-13 has been identified. Here, we show that mutations in the CYLD gene are also the genetic basis for three different Chinese families with MFT. Sequence analysis reveal a single nucleotide deletion, c.1462delA (P.Ile488fsX9) in exon 9, a nonsense mutation, c.2128C>T (p. Gln710X) in exon 17, and a missense mutation, c.2822A>T (p. Asp941Val) in exon 21 in each of the three families respectively. This provides direct evidence that the mutations in CYLD can cause two clinically distinct cancer syndromes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • China
  • Chromosomes, Human, Pair 9
  • Deubiquitinating Enzyme CYLD
  • Female
  • Genetic Linkage
  • Humans
  • Loss of Heterozygosity
  • Male
  • Mutation*
  • Neoplasms, Basal Cell / genetics*
  • Neoplasms, Basal Cell / pathology
  • Pedigree
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Tumor Suppressor Proteins / genetics*

Substances

  • Tumor Suppressor Proteins
  • CYLD protein, human
  • Deubiquitinating Enzyme CYLD