Adaptor Proteins, Signal Transducing/genetics* ; Asian Continental Ancestry Group/genetics ; Codon, Terminator ; Colorectal Neoplasms/genetics* ; Colorectal Neoplasms, Hereditary Nonpolyposis/genetics* ; Exons ; Family ; Female ; Frameshift Mutation ; Germ-Line Mutation ; Humans ; Korea ; Male ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein/genetics* ; Mutation, Missense* ; Nuclear Proteins/genetics* ; Pedigree
Abstract
Hereditary nonpolyposis colorectal cancer (HNPCC) (MIM #114500), also called Lynch syndrome, is an autosomal dominantly inherited cancer syndrome accounting for 1-5% of all colorectal cancer cases. In a study of three Korean families with HNPCC consistent with the revised Bethesda criteria, DNA testing revealed three novel HNPCC germline mutations in two genes: namely, MLH1, with an insertion resulting in a frameshift and a premature stop codon; MSH2, with a deletion at nucleotide 633, exon 3, which results in stop of translation at codon 213; and MSH2, with a deletion at nucleotide 1413, exon 9, resulting in a frameshift and a premature stop codon. In the first two families, there were splice mutations at c.2006-6 thymine to cytosine. The clinical implications of a frameshift mutation are discussed, along with the significance of common underlying splice mutations existing within families with HNPCC