title: A truncated hMSH2 transcript occurs as a common variant in the population: implications for genetic diagnosis.
abstract: Germline mutations of the hMSH2 gene are responsible for many cases of hereditary nonpolyposis colorectal cancer. While screening for hMSH2 gene mutations in hereditary nonpolyposis colorectal cancer kindreds, we observed that a previously reported germline mutation is in fact a common, alternatively spliced variant in the population. Using RT-PCR and the protein truncation test, the hMSH2 exon 13 deletion variant was found in more than 90% of individuals. The exon 13 deletion transcript was only present in lymphocyte RNA, no abnormalities were detected in genomic DNA flanking exon 13, and the deletion transcript is apparently not translated. These findings highlight further that caution should be exercised in providing genetic risk assessment on the basis of currently used germline mutation detection strategies.
authors.affiliation: Department of Pathology, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Xia
authors.forename: W
authors.initials: W
authors.lastname: Shen
authors.forename: F
authors.initials: F
authors.lastname: Ritacca
authors.forename: A
authors.initials: A
authors.lastname: Mitri
authors.forename: L
authors.initials: L
authors.lastname: Madlensky
authors.forename: T
authors.initials: T
authors.lastname: Berk
authors.forename: Z
authors.initials: Z
authors.lastname: Cohen
authors.forename: S
authors.initials: S
authors.lastname: Gallinger
authors.forename: B
authors.initials: B
authors.lastname: Bapat
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics / Q000517:prevention & control*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005189:False Positive Reactions; D005656:Fungal Proteins; D015972:Gene Expression Regulation, Neoplastic; D005817:Genetic Counseling; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D018570:Risk Assessment; D017384:Sequence Deletion
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051718:MutS Homolog 2 Protein