title: Three novel mutations of the NF1 gene detected by temperature gradient gel electrophoresis of exons 5 and 8.
abstract: We screened a total of 100 unrelated patients with neurofibromatosis type 1 (NF1) for mutations on exons 5 and 8 of the NF1 gene using temperature gradient gel electrophoresis (TGGE). Careful interpretation of exon 5 TGGE patterns was necessary due to interference by an exonic polymorphism. Three novel mutations were identified: a stop mutation in exon 5 (Q239X) caused by a C-->T transition at cDNA nucleotide position 715, a transition at the invariant G of the splice acceptor site in the intron 4c (G655-1A), and a transversion at the invariant G of the splice donor site in intron 8 (G1185 + 1T). Analysis of mRNA revealed the predicted abnormal splice products. While skipping of exon 5 causes a shift in the reading frame with a premature stop codon downstream in the middle of exon 6, skipping of exon 8 leads to an in-frame deletion with the predicted protein product being shortened by 41 amino acids.
authors.affiliation: Institut für Medizinische Genetik, Universitätsklinikum Charité, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Horn
authors.forename: P N
authors.initials: PN
authors.lastname: Robinson
authors.forename: A
authors.initials: A
authors.lastname: Böddrich
authors.forename: A
authors.initials: A
authors.lastname: Buske
authors.forename: S
authors.initials: S
authors.lastname: Tinschert
authors.forename: P
authors.initials: P
authors.lastname: Nürnberg
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D016514:Genes, Neurofibromatosis 1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D013696:Temperature
chemical_list: D012333:RNA, Messenger