title: Analysis of CpG C-to-T mutations in neurofibromatosis type 1. Mutations in brief no. 129. Online.
abstract: Neurofibromatosis type 1 (NF1) is a dominant disorder caused by mutations in the NF1 gene; approximately 100 NF1 gene mutations have been published. The CpG C-to-T transition is a frequent mutation mechanism in genetic disorders. To estimate its frequency in NF1, we employed a PCR-restriction digestion method to examine 17 CpGs in 65 patients, and also screened for a CpG nonsense transition (R1947X) that occurs in 1-2% of patients. The analysis revealed disease-related CpG C-to-T transitions (including a nonsense mutation that may be as frequent as R1947X) as well as a benign variant and another mutation at a CpG. Four patients showed CpG mutations in analysis of 18 sites (17 surveyed by restriction digest, plus the R1947X assay), including three C-to-T transitions and one C-to-G transversion. These 18 sites represent one-fifth of the 91 CpGs at which a C-to-T transition would result in a nonsense or nonconservative missense mutation. Thus, it is feasible that the CpG mutation rate at NF1 might be similar to that seen in other disorders with a high mutation rate, and that recurrent NF1 mutations may frequently reside at CpG sites.
authors.affiliation: Department of Pediatrics, Division of Genetics, University of Florida, Gainesville, Florida, USA.
authors.forename: S
authors.initials: S
authors.lastname: Krkljus
authors.forename: C R
authors.initials: CR
authors.lastname: Abernathy
authors.forename: J S
authors.initials: JS
authors.lastname: Johnson
authors.forename: C A
authors.initials: CA
authors.lastname: Williams
authors.forename: D J
authors.initials: DJ
authors.lastname: Driscoll
authors.forename: R
authors.initials: R
authors.lastname: Zori
authors.forename: H J
authors.initials: HJ
authors.lastname: Stalker
authors.forename: S A
authors.initials: SA
authors.lastname: Rasmussen
authors.forename: F S
authors.initials: FS
authors.lastname: Collins
authors.forename: B G
authors.initials: BG
authors.lastname: Kousseff
authors.forename: L
authors.initials: L
authors.lastname: Baumbach
authors.forename: M R
authors.initials: MR
authors.lastname: Wallace
mesh_terms: D003596:Cytosine; D016514:Genes, Neurofibromatosis 1 / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000235:genetics*; D013941:Thymine
chemical_list: D003596:Cytosine; D013941:Thymine