Abstract
Affected and unaffected members of a Caucasian family with Werner syndrome were analyzed for mutations in the recently described Werner syndrome (WRN) gene and for their relevance to phenotypic expression of chromosomal instability and x-ray hypersensitivity. Two distinct molecular alterations were documented in the family. Analysis of the genomic DNA revealed a single-base exchange from A to T at an intron-exon boundary in the otherwise strongly conserved 5′ donor splice site. Consequently, exon 30 is spliced together with the intron. The ensuing structure could be confirmed by the presence and calculated size of the resulting RNA fragments. The patients, all compound heterozygotes, had a 1-bp deletion in the first third of the coding sequence in the other allele. The genotypes of the family members for these mutations were determined and consequences for the cellular phenotype of the otherwise unaffected heterozygotes are documented.
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Acknowledgements
We are indebted to the Thyssen-Stiftung and to the ‘Fonds der Chemischen Industrie’ for financial support. The work was further supported by the ‘Deutsche Forschungsgemeinschaft’ SCHW 532/2-1 and by the ‘Österreichische Nationalbank, Jubiläumsfonds 4842’. Determination of hyaluronate in urine was performed by Dr. H. Greiling, Aachen, Germany. We are also grateful to Dr. D.H. Kauffmann Jockl, New York, N.Y., for critical reading and improving the manuscript.
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Meißlitzer, C., Ruppitsch, W., Weirich-Schwaiger, H. et al. Werner Syndrome: Characterization of Mutations in the WRN Gene in an Affected Family. Eur J Hum Genet 5, 364–370 (1997). https://doi.org/10.1007/BF03405944
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DOI: https://doi.org/10.1007/BF03405944
