title: Paternal germ cell mosaicism in autosomal dominant pachyonychia congenita.
abstract: BACKGROUND
  Pachyonychia congenita (PC) is a genodermatosis caused by mutations in 1 of 4 known keratin genes, including KRT6A, KRT6B, KRT16, or KRT17. The most common mode of inheritance is autosomal dominant. Families with an affected parent are routinely counseled about the 50% transmission risk to each offspring. In some cases, families with a rare disorder like PC can initially present with an affected child while both parents are unaffected. This is usually the result of a spontaneous in utero mutation, and the risk of subsequent offspring being affected with the same condition is negligible (but may be increased above the general population's risk, although the exact risk is not currently known for PC).
  
  
  METHODS
  We discuss a case of 2 affected children born to unaffected parents. We performed mutational analyses of all 4 individuals in the family on DNA extracted from lymphocytes. Owing to the unusual presentation of 2 affected siblings, we also extracted DNA from the father's sperm cells for keratin gene mutational analysis. We describe the first case, to our knowledge, of germ cell mosaicism in PC.
  
  
  CONCLUSIONS
  Counseling of unaffected parents with a first child diagnosed as having PC should entail a discussion of the possibility of germ cell mosaicism contributing to an increased risk of having subsequent affected children.
authors.affiliation: Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
authors.forename: Lana N
authors.initials: LN
authors.lastname: Pho
authors.forename: Frances J D
authors.initials: FJ
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Konecki
authors.forename: Sherri
authors.initials: S
authors.lastname: Bale
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: Bernard
authors.initials: B
authors.lastname: Cohen
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Eliason
authors.forename: Sancy A
authors.initials: SA
authors.lastname: Leachman
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D007633:Keratins / Q000235:genetics*; D008297:Male; D009030:Mosaicism; D053549:Pachyonychia Congenita / Q000235:genetics* / Q000473:pathology
chemical_list: D007633:Keratins