title: Identification and characterization of NF1 splicing mutations in Korean patients with neurofibromatosis type 1.
abstract: Neurofibromatosis type I (NF1) is an autosomal dominant genetic disorder caused by NF1 mutations. Although mutations affecting mRNA splicing are the most common molecular defects in NF1, few studies have analyzed genomic DNA (gDNA)-mRNA correlations in Korean NF1 patients. In this study, we investigated 28 unrelated NF1 patients who showed splicing alterations in reverse transcription-PCR of NF1 mRNA and identified 24 different NF1 splicing mutations, 9 of which were novel. These mutations can be categorized into five groups: exon skipping resulting from mutations at authentic 5' and 3' splice sites (type I, 46%), cryptic exon inclusion caused by deep intronic mutations (type II, 8%), creation of new splice sites causing loss of exonic sequences (type III, 8%), activation of cryptic splice sites due to disruption of authentic splice sites (type IV, 25%) and exonic sequence alterations causing exon skipping (type V, 13%). In total, 42% of all splicing mutations did not involve the conserved AG/GT dinucleotides of the splice sites, making it difficult to identify the correct mutation sites at the gDNA level. These results add to the mutational spectrum of NF1 and further elucidate the gDNA-mRNA correlations of NF1 mutations.
authors.affiliation: Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea.
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Jang
authors.affiliation: Green Cross Genome, Yongin, Republic of Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Kyung
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Myoung-Keun
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Chang-Seok
authors.identifier: http://orcid.org/0000-0001-7679-8731
authors.initials: CS
authors.lastname: Ki
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D019943:Amino Acid Substitution; D019295:Computational Biology / Q000379:methods; D005091:Exons; D016514:Genes, Neurofibromatosis 1; D005838:Genotype; D006801:Humans; D007438:Introns; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D012326:RNA Splicing; D056910:Republic of Korea; D012189:Retrospective Studies