title: A 'nonsense' mutation leads to aberrant splicing of hMLH1 in a German hereditary non-polyposis colorectal cancer family.
abstract: Hereditary Non-polyposis Colorectal Cancer (HNPCC) is an autosomal dominant cancer predisposition syndrome caused by germline mutations in at least four genes encoding integral components of the cellular DNA mismatch repair (MMR) system. The spectrum of genetic alterations encompasses missense- and nonsense mutations, intronic mutations affecting splice donor or acceptor sites as well as small-scale deletions and insertions. We have identified a 'nonsense' mutation that activates a cryptic splice site generating an in frame deletion of the last 17 codons of exon1 of the hMLH1 gene causing HNPCC in a German family. We present a comprehensive genetic analysis of this family that demonstrates important aspects of HNPCC pathogenesis.
authors.affiliation: Department of General Surgery, University of Heidelberg, INF 110, Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Baehring
authors.forename: C
authors.initials: C
authors.lastname: Sutter
authors.forename: M
authors.initials: M
authors.lastname: Kadmon
authors.forename: M V Knebel
authors.initials: MV
authors.lastname: Doeberitz
authors.forename: J
authors.initials: J
authors.lastname: Gebert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D018389:Codon, Nonsense; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D006801:Humans; D008297:Male; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D012326:RNA Splicing
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018389:Codon, Nonsense; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1