title: Werner syndrome: characterization of mutations in the WRN gene in an affected family.
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.
authors.affiliation: Institut für Biochemie, Freie Universität Berlin, Deutschland.
authors.forename: C
authors.initials: C
authors.lastname: Meisslitzer
authors.forename: W
authors.initials: W
authors.lastname: Ruppitsch
authors.forename: H
authors.initials: H
authors.lastname: Weirich-Schwaiger
authors.forename: H G
authors.initials: HG
authors.lastname: Weirich
authors.forename: J
authors.initials: J
authors.lastname: Jabkowsky
authors.forename: G
authors.initials: G
authors.lastname: Klein
authors.forename: M
authors.initials: M
authors.lastname: Schweiger
authors.forename: M
authors.initials: M
authors.lastname: Hirsch-Kauffmann
mesh_terms: D000328:Adult; D019588:Aging, Premature / Q000235:genetics; D001317:Austria; D002869:Chromosome Aberrations; D019457:Chromosome Breakage / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005090:Exodeoxyribonucleases; D005260:Female; D005347:Fibroblasts; D005838:Genotype; D006801:Humans; D008214:Lymphocytes; D008297:Male; D015162:Micronucleus Tests; D010375:Pedigree; D010641:Phenotype; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis; D053484:RecQ Helicases; D014898:Werner Syndrome / Q000235:genetics*; D000071657:Werner Syndrome Helicase; D044465:White People; D014965:X-Rays
chemical_list: D012333:RNA, Messenger; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase