title: A novel compound heterozygous mutation in Werner syndrome results in WRN transcript decay.
abstract: BACKGROUND
  Werner syndrome (WS) is a rare autosomal recessive progeroid disorder caused by mutations of the WRN gene encoding a protein of the RecQ-type family of DNA helicases.
  
  
  OBJECTIVE
  To develop a rapid and simple reverse transcription-polymerase chain reaction (RT-PCR) strategy for mutation analysis of the WRN gene, to identify pathogenic mutations in a German patient with WS and to determine the effects of the pathogenic mutations on WRN mRNA stability.
  
  
  METHODS
  Allele-specific RT-PCR, semiquantitative RT-PCR, DNA sequencing.
  
  
  RESULTS
  We describe a novel and rapid RT-PCR-based method for mutation analysis in WS and report a German patient with WS carrying a previously reported (1396delA) as well as a novel nonsense mutation (2334delAC) of the WRN gene. By semiquantitative RT-PCR analysis we demonstrate that this compound heterozygous genotype leads to WRN transcript decay.
  
  
  CONCLUSIONS
  In previous studies WS was primarily attributed to a loss of function of stable truncated WRN gene products. Our findings indicate that mutations can also lead to markedly decreased WRN transcript stability.
authors.affiliation: Department of Dermatology, University of Cologne, Kerpener Str. 62, 50937 Köln, Germany. felix.mueller@uni-koeln.de
authors.forename: F B
authors.initials: FB
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Tsianakas
authors.forename: C
authors.initials: C
authors.lastname: Kuwert
authors.forename: B P
authors.initials: BP
authors.lastname: Korge
authors.forename: N
authors.initials: N
authors.lastname: Hunzelmann
mesh_terms: D001483:Base Sequence; D018389:Codon, Nonsense; D004265:DNA Helicases / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005090:Exodeoxyribonucleases; D019066:Facies; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D053484:RecQ Helicases; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods; D014898:Werner Syndrome / Q000235:genetics*; D000071657:Werner Syndrome Helicase
chemical_list: D018389:Codon, Nonsense; D018076:DNA, Complementary; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase