A novel compound heterozygous mutation in Werner syndrome results in WRN transcript decay.
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.
Müller
F B
FB
Department of Dermatology, University of Cologne, Kerpener Str. 62, 50937 Köln, Germany. felix.mueller@uni-koeln.de
Tsianakas
A
A
Kuwert
C
C
Korge
B P
BP
Hunzelmann
N
N
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
D018389:Codon, Nonsense; D018076:DNA, Complementary; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase