title: Homozygosity for the c.917A→T (p.N306l) polymorphism in the EVER2/TMC8 gene of two sisters with epidermodysplasia verruciformis Lewandowsky-Lutz originally described by Wilhelm Lutz.
abstract: BACKGROUND
  Epidermodysplasia verruciformis Lewandowsky-Lutz (EV) is a rare genodermatosis, characterised by development of numerous verrucous skin lesions caused by specific genotypes of human papillomaviruses belonging to the β-papillomavirus genus. The EV loci were mapped to chromosome 2p21-p24 (EV2) and 17q25 (EV1). On chromosome 17, 2 adjacent related genes--EVER1/TMC6 and EVER2/TMC8--were identified. We reinvestigated 2 patients originally described by Wilhelm Lutz in 1946 with the aim to document the natural course of the disease and confirm his diagnosis.
  
  
  METHODS
  PCR fragments specific for exons with short flanking intron sequences of EVER1/TMC6 and EVER2/TMC8 genes from patients' DNA were amplified using sequence information. The single-nucleotide polymorphism (SNP) rs7208422 was studied, using restriction fragment length polymorphism analysis.
  
  
  RESULTS
  In the index patient, we identified a homozygous TT genotype in exon 8 of the EVER2/TMC8 gene (c.917A→T, p.N306I). The same mutation could thereafter be detected in her sister from paraffin-embedded skin.
  
  
  CONCLUSIONS
  We have followed one of the first patients described with EV in Basel, Switzerland, in 1930 until today and demonstrated the TT genotype (SNP rs7208422) in the EVER2/TMC8 gene in this index patient and her sister. The results underline the possible relevance of SNP rs7208422 by influencing the susceptibility to β-papillomaviruses and their oncogenic potential.
authors.affiliation: Department of Dermatology, University Hospital Basel, Basel, Switzerland. aarnold@uhbs.ch
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Arnold
authors.forename: Bettina
authors.initials: B
authors.lastname: Burger
authors.forename: Erwin
authors.initials: E
authors.lastname: Kump
authors.forename: Alexander
authors.initials: A
authors.lastname: Rufle
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Tyring
authors.forename: Werner
authors.initials: W
authors.lastname: Kempf
authors.forename: Peter
authors.initials: P
authors.lastname: Häusermann
authors.forename: Peter H
authors.initials: PH
authors.lastname: Itin
mesh_terms: D000369:Aged, 80 and over; D052686:Betapapillomavirus; D002277:Carcinoma / Q000235:genetics / Q000821:virology*; D002886:Chromosomes, Human, Pair 17; D004252:DNA Mutational Analysis; D004819:Epidermodysplasia Verruciformis / Q000235:genetics* / Q000821:virology; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D012878:Skin Neoplasms / Q000235:genetics / Q000821:virology*