title: Keratin 17 mutation in pachyonychia congenita type 2 with early onset sebaceous cysts.
abstract: BACKGROUND
  Pachyonychia congenita (PC) is a group of autosomal dominant ectodermal dysplasias caused by mutations in four differentiation-specific keratin genes. Two major clinical subtypes of PC have been generally recognized. Symmetrically thickened fingernails and toenails are the defining characteristic of PC type 2 (PC-2) with onset at infancy. Pilosebaceous cysts are the best hallmark of PC-2, but they usually occur at puberty.
  
  
  OBJECTIVE
  To report a Chinese pedigree of PC-2 with unusually early onset sebaceous cysts and to explore the genetic mutation and its phenotype.
  
  
  METHODS
  Exon 1 of keratin 17 was amplified by polymerase chain reaction (PCR) from genomic DNA from the three patients in the pedigree, the proband, his half-sister and his younger son, two unaffected members in the pedigree and 50 unrelated and unaffected people. PCR products were directly sequenced to detect the mutation.
  
  
  RESULTS
  Direct sequencing of the PCR products revealed a heterozygous 275A-->G mutation in all three affected members. This mutation predicts the substitution of asparagine by serine in codon 92 (N92S) located in the 1A domain of keratin 17.
  
  
  CONCLUSIONS
  Mutation in the 1A domain of keratin 17 underlies the affected members' phenotype, PC-2 with early onset sebaceous cysts and late-onset thickened fingernails and toenails. The onset of the cysts is very early in some people within this family and the age at onset of thickened fingernails and toenails is variable within the family, implying the existence of modifying factors.
authors.affiliation: Department of Dermatology, the Second Hospital, Xi'an Jiaotong University, 157 Xiwu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Y-G
authors.initials: YG
authors.lastname: Feng
authors.forename: S-X
authors.initials: SX
authors.lastname: Xiao
authors.forename: X-R
authors.initials: XR
authors.lastname: Ren
authors.forename: W-Q
authors.initials: WQ
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Pan
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002681:China; D004476:Ectodermal Dysplasia / Q000150:complications / Q000235:genetics*; D004814:Epidermal Cyst / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007633:Keratins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009264:Nails, Malformed / Q000150:complications / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012871:Skin Diseases / Q000150:complications / Q000235:genetics*
chemical_list: D007633:Keratins